Akiko Iwasaki, PhD
Research & Publications
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Research Summary
The mucosal surfaces represent major sites of entry for numerous infectious agents. Consequently, the vast mucosal surfaces are intricately lined with cells and lymphoid organs specialized in providing protective antibody and cellular immunity. We focus on understanding how viruses are recognized by the cells of the innate immune system and how that information is used to generate protective adaptive immunity. We study immune responses to herpes simplex viruses and Zika viruses in the genital tract and influenza virus and rhinovirus infection in the lung. Our studies probe the mechanism of protection provided by the memory T cells that reside within the mucosal organs, known as tissue resident memory T cells, and use this information to design better vaccines. We developed a new vaccine strategy, "Prime and Pull" in which memory T cells can be established at the mucosal surface targeted by viruses. Prime and Pull confers better protection against genital herpes than conventional vaccine approaches. Our ultimate goal is to utilize the knowledge we gain through these areas of research in the rational design of effective vaccines or microbicides for the prevention of transmission of viral pathogens and possible treatment of cancers.
Specialized Terms: Innate immunity; Autophagy; Inflammasomes; Sexually transmitted infections; Herpes simplex virus; Human papillomavirus; Respiratory virus infections; Influenza infection; T cell immunity; Commensal bacteria
Extensive Research Description
Our research addresses mechanisms of innate recognition of viruses and initiation of antiviral immunity, particularly at the natural site of virus encounter at the mucosal surfaces.
Innate virus recognition, autophagy and signaling: The innate immune system has evolved to recognize invading pathogens through pattern recognition receptors (PRRs). Because viruses are synthesized by the host cell machinery, the nature of viral signatures recognized by PRRs was unclear. Our research revealed that viral nucleic acids from dsDNA and ssRNA viruses serve as a viral signature, and that they are recognized by endosomal Toll-like receptors (TLR)-9 and TLR-7, respectively in plasmacytoid dendritic cells (pDCs). Further, we demonstrated that in vivo, pDCs are required to secrete type I IFNs in response to genital herpes infection and mediate innate protection of the host. We discovered the role of autophagy in innate viral recognition. We demonstrated that TLR-7-mediated recognition of certain ssRNA viruses requires transport of cytosolic viral replication intermediates into the endosome by the process of autophagy in pDCs. This study demonstrated a link between innate viral recognition and autophagy. Unlike the pDCs, most other cell types recognize virus infection via the RIG-I-like receptors (RLRs) within the cytosol. In a recent study, we demonstrated that autophagy regulates RLR pathway by removal of damaged mitochondria. In the absence of autophagy, reactive oxygen species (ROS) accumulate within the mitochondria, and turn off regulation of RLR signaling. Thus, autophagy is essential in 1) delivering viral ligands to endosomal TLRs, and 2) clearing damaged mitochondria and ROS, thus regulating RLR signaling. We are currently investigating the mechanism by which ROS regulates RLR signaling. More recently, we identified a lysosome-related organelle from which both TLR7 and TLR9 traffic to signal for interferon production and demonstrated that TLR traffic to this compartment is mediated by the adaptor protein AP-3. AP-3 recruitment to the TLR9 endosome requires activity of PIKfyve, an enzyme that phosphorylates PI3P to form PI(3,5)P2 on endosomal membrane.
Temperature control of innate immune response to viruses: we found that temperature can alter the ability of the airway cells to mount an effective innate immune response against rhinovirus, the common cold virus. Airway epithelial cells, the cells that form the lining of the nose and the other airways, are the main target of rhinovirus infection. In order to amplify, spread, and cause disease, the virus must enter these cells and make more copies of itself. By studying airway cells incubated at different temperatures, we discovered that mechanisms used by the innate immune system to protect cells against this virus are quite effective at core body temperature (37°C), but are greatly diminished at slightly cooler temperatures, such as temperatures that might be found in the nasal passages upon inhaling cool ambient air (33°C). The temperature-dependent signals included those involved in the recognition of the replicating virus inside the cell (the RIG-I like receptor pathway) as well as the signals required for turning on antiviral defenses following viral recognition (the Type I interferon response.) These signals are important in immune defense against many viruses, and future studies may reveal that lower temperature provides an opportunity for other viruses that infect the airways or other cool areas of the body to evade antiviral defenses.
Adaptive immunity to viruses: Innate recognition of viruses allows activation of adaptive immune responses. Dendritic cells (DCs) are potent inducers of T cell responses. However, how various populations of DCs sense virus infection and induce immune responses during a natural virus infection is unclear. OUr study demonstrated that submucosal DCs (beneath the epithelial layer), but not Langerhans cells (within the epithelial layer), are the primary inducers of Th1 immunity following genital herpes infection. Antigen presentation following mucosal viral infection is handled by the tissue-migrant submucosal DCs, while needle-introduced virus antigens are presented by lymphoid resident DCs . In addition to the direct activation of DCs by TLRs, we showed that DCs require TLR-dependent instructive signals from the infected cells in order to induce differentiation of effector T cells. We further demonstrated the requirement for TLR-dependent signal in enabling maximum screening of cognate lymphocytes during initiation of adaptive immunity through remodeling of the lymph node arteriole. Once initiated within the lymph nodes, effector Th1 cells travel to the site of infection and eliminate virus infection. Our recent study showed that the local mucosal DCs and B cells cooperate to restimulate Th1 cells to execute protective antiviral immunity. These studies collectively demonstrated the importance of tissue-DC interaction in the initiation of antiviral immunity. While the role of TLRs and RLRs in the initiation of adaptive immunity has been studied extensively, the role of NOD-like receptors (NLRs) in innate viral recognition and initiation of adaptive immune responses is unknown. Our recent study demonstrated that influenza virus infection triggers NLRs and it is required to elicit protective T cell and B cell immunity. We are currently using this information to design and develop novel vaccine strategies to better fight viral infections including HSV-2, influenza and human papillomavirus.
Tissue resident memory T cells: Adaptive immune response to pathogens generates effector T cells with diverse functions. While the majority of effector T cells engage in pathogen control during primary infection, a subset of effector T cells differentiates into memory T cells critical for controlling future infections. Recent studies have revealed that a small subset of effector T cells seed the lymphoid and non-lymphoid tissues and establish residency. Precursors of tissue-resident memory T cells (TRM) receive critical cues from the tissue for migration and residency. We demonstrated that CD4 T cells 'help" the CD8 T effector cells enter the tissue through their secretion of IFN-g and induction of CXCL9 and CXCL10 that bind to CXCR3 expressed by teh CD8 effector T cells. We also demonstrated that TRM can reside within the epithelial layer, or be housed subepithelially in a structure known as memory lymphocyte clusters (MLCs). MLCs are self-sustaining home to the TRMand are supported by the local macrophages that secrete retention signals. Importantly, CD4 and CD8 TRM provide potent protection against viral challenge compared to circulating memory counterparts. Based on this understanding, we developed a new vaccine strategy we call "Prime and Pull". This vaccine works in two steps. First, we prime T cell responses using conventional vaccines. Second, we "pull" in the T cells to the organ of choice using chemokines that we now know are capable of recruiting such cells (CXCL9 and CXCL10). The Prime and Pull vaccine provides much better protection against genital herpes infection than conventional vaccine alone, because it establishes CD8 TRM at the site of pathogen entry. This understanding for CD8 T cell access can be harnessed to enable T cell entry into solid tumors, which has direct implications for cancer immunotherapy.
Coauthors
Research Interests
Arboviruses; Autophagy; DNA Viruses; Herpes Simplex; Immune System; Immunity, Cellular; Immunity, Innate; Influenza, Human; Molecular Biology; Pneumonia, Viral; Pregnancy Complications; Proviruses; RNA Viruses; Sexually Transmitted Diseases; Tumor Virus Infections; Encephalitis, Viral; Central Nervous System Viral Diseases; Inflammasomes
Public Health Interests
Vaccines
Selected Publications
- IL-7R licenses a population of epigenetically poised memory CD8+ T cells with superior antitumor efficacy that are critical for melanoma memoryMicevic G, Daniels A, Flem-Karlsen K, Park K, Talty R, McGeary M, Mirza H, Blackburn H, Sefik E, Cheung J, Hornick N, Hornick N, Aizenbud L, Joshi N, Kluger H, Iwasaki A, Bosenberg M, Bosenberg M, Flavell R. IL-7R licenses a population of epigenetically poised memory CD8+ T cells with superior antitumor efficacy that are critical for melanoma memory. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2304319120. PMID: 37459511, PMCID: PMC10372654, DOI: 10.1073/pnas.2304319120.
- Cytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine–associated myocarditisBarmada A, Klein J, Ramaswamy A, Brodsky N, Jaycox J, Sheikha H, Jones K, Habet V, Campbell M, Sumida T, Kontorovich A, Bogunovic D, Oliveira C, Steele J, Hall E, Pena-Hernandez M, Monteiro V, Lucas C, Ring A, Omer S, Iwasaki A, Yildirim I, Lucas C. Cytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine–associated myocarditis. Science Immunology 2023, 8: eadh3455. PMID: 37146127, PMCID: PMC10468758, DOI: 10.1126/sciimmunol.adh3455.
- Enhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariantsMoriyama M, Lucas C, Monteiro V, Initiative Y, Iwasaki A, Chen N, Breban M, Hahn A, Pham K, Koch T, Chaguza C, Tikhonova I, Castaldi C, Mane S, De Kumar B, Ferguson D, Kerantzas N, Peaper D, Landry M, Schulz W, Vogels C, Grubaugh N. Enhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2221652120. PMID: 37036977, PMCID: PMC10120007, DOI: 10.1073/pnas.2221652120.
- Nonsystematic Reporting Biases of the SARS-CoV-2 Variant Mu Could Impact Our Understanding of the Epidemiological Dynamics of Emerging VariantsPetrone M, Lucas C, Menasche B, Breban M, Yildirim I, Campbell M, Omer S, Holmes E, Ko A, Grubaugh N, Iwasaki A, Wilen C, Vogels C, Fauver J. Nonsystematic Reporting Biases of the SARS-CoV-2 Variant Mu Could Impact Our Understanding of the Epidemiological Dynamics of Emerging Variants. Genome Biology And Evolution 2023, 15: evad052. PMID: 36974986, PMCID: PMC10113931, DOI: 10.1093/gbe/evad052.
- Pharmacological disruption of mSWI/SNF complex activity restricts SARS-CoV-2 infectionWei J, Patil A, Collings C, Alfajaro M, Liang Y, Cai W, Strine M, Filler R, DeWeirdt P, Hanna R, Menasche B, Ökten A, Peña-Hernández M, Klein J, McNamara A, Rosales R, McGovern B, Luis Rodriguez M, García-Sastre A, White K, Qin Y, Doench J, Yan Q, Iwasaki A, Zwaka T, Qi J, Kadoch C, Wilen C. Pharmacological disruption of mSWI/SNF complex activity restricts SARS-CoV-2 infection. Nature Genetics 2023, 55: 471-483. PMID: 36894709, PMCID: PMC10011139, DOI: 10.1038/s41588-023-01307-z.
- SARS-CoV-2 mRNA vaccines decouple anti-viral immunity from humoral autoimmunityJaycox J, Lucas C, Yildirim I, Dai Y, Wang E, Monteiro V, Lord S, Carlin J, Kita M, Buckner J, Ma S, Campbell M, Ko A, Omer S, Lucas C, Speake C, Iwasaki A, Ring A. SARS-CoV-2 mRNA vaccines decouple anti-viral immunity from humoral autoimmunity. Nature Communications 2023, 14: 1299. PMID: 36894554, PMCID: PMC9996559, DOI: 10.1038/s41467-023-36686-8.
- Type 2 Dendritic Cells Orchestrate a Local Immune Circuit to Confer Antimetastatic ImmunityWeizman O, Luyten S, Krykbaeva I, Song E, Mao T, Bosenberg M, Iwasaki A. Type 2 Dendritic Cells Orchestrate a Local Immune Circuit to Confer Antimetastatic Immunity. The Journal Of Immunology 2023, 210: 1146-1155. PMID: 36881866, PMCID: PMC10067787, DOI: 10.4049/jimmunol.2200697.
- Response to: Elevated L1 expression in ataxia telangiectasia likely explained by an RNA-seq batch effectTakahashi T, Stoiljkovic M, Song E, Gao X, Yasumoto Y, Kudo E, Carvalho F, Kong Y, Park A, Shanabrough M, Szigeti-Buck K, Liu Z, Kristant A, Zhang Y, Sulkowski P, Glazer P, Kaczmarek L, Horvath T, Iwasaki A. Response to: Elevated L1 expression in ataxia telangiectasia likely explained by an RNA-seq batch effect. Neuron 2023, 111: 612-613. PMID: 36863323, DOI: 10.1016/j.neuron.2023.02.006.
- Why we need a deeper understanding of the pathophysiology of long COVIDIwasaki A, Putrino D. Why we need a deeper understanding of the pathophysiology of long COVID. The Lancet Infectious Diseases 2023 PMCID: PMC9928485, DOI: 10.1016/s1473-3099(23)00053-1.
- Why we need a deeper understanding of the pathophysiology of long COVIDIwasaki A, Putrino D. Why we need a deeper understanding of the pathophysiology of long COVID. The Lancet Infectious Diseases 2023, 23: 393-395. PMID: 36967698, PMCID: PMC9928485, DOI: 10.1016/s1473-3099(23)00053-1.
- Mature B cells and mesenchymal stem cells control emergency myelopoiesisLim V, Feng X, Miao R, Zehentmeier S, Ewing-Crystal N, Lee M, Tumanov A, Oh J, Iwasaki A, Wang A, Choi J, Pereira J. Mature B cells and mesenchymal stem cells control emergency myelopoiesis. Life Science Alliance 2023, 6: e202301924. PMID: 36717247, PMCID: PMC9889502, DOI: 10.26508/lsa.202301924.
- PD-1highCXCR5–CD4+ peripheral helper T cells promote CXCR3+ plasmablasts in human acute viral infectionAsashima H, Mohanty S, Comi M, Ruff W, Hoehn K, Wong P, Klein J, Lucas C, Cohen I, Coffey S, Lele N, Greta L, Raddassi K, Chaudhary O, Unterman A, Emu B, Kleinstein S, Montgomery R, Iwasaki A, Dela Cruz C, Kaminski N, Shaw A, Hafler D, Sumida T. PD-1highCXCR5–CD4+ peripheral helper T cells promote CXCR3+ plasmablasts in human acute viral infection. Cell Reports 2023, 42: 111895. PMID: 36596303, PMCID: PMC9806868, DOI: 10.1016/j.celrep.2022.111895.
- Plasmodium infection is associated with cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike proteinLapidus S, Liu F, Casanovas-Massana A, Dai Y, Huck J, Lucas C, Klein J, Filler R, Strine M, Sy M, Deme A, Badiane A, Dieye B, Ndiaye I, Diedhiou Y, Mbaye A, Diagne C, Vigan-Womas I, Mbengue A, Sadio B, Diagne M, Moore A, Mangou K, Diallo F, Sene S, Pouye M, Faye R, Diouf B, Nery N, Costa F, Reis M, Muenker M, Hodson D, Mbarga Y, Katz B, Andrews J, Campbell M, Srivathsan A, Kamath K, Baum-Jones E, Faye O, Sall A, Vélez J, Cappello M, Wilson M, Ben-Mamoun C, Tedder R, McClure M, Cherepanov P, Somé F, Dabiré R, Moukoko C, Ouédraogo J, Boum Y, Shon J, Ndiaye D, Wisnewski A, Parikh S, Iwasaki A, Wilen C, Ko A, Ring A, Bei A. Plasmodium infection is associated with cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein. Scientific Reports 2022, 12: 22175. PMID: 36550362, PMCID: PMC9778468, DOI: 10.1038/s41598-022-26709-7.
- Association between primary or booster COVID-19 mRNA vaccination and Omicron lineage BA.1 SARS-CoV-2 infection in people with a prior SARS-CoV-2 infection: A test-negative case–control analysisLind M, Robertson A, Silva J, Warner F, Coppi A, Price N, Duckwall C, Sosensky P, Di Giuseppe E, Borg R, Fofana M, Ranzani O, Dean N, Andrews J, Croda J, Iwasaki A, Cummings D, Ko A, Hitchings M, Schulz W. Association between primary or booster COVID-19 mRNA vaccination and Omicron lineage BA.1 SARS-CoV-2 infection in people with a prior SARS-CoV-2 infection: A test-negative case–control analysis. PLOS Medicine 2022, 19: e1004136. PMID: 36454733, PMCID: PMC9714718, DOI: 10.1371/journal.pmed.1004136.
- Serological fingerprints link antiviral activity of therapeutic antibodies to affinity and concentrationFiedler S, Devenish S, Morgunov A, Ilsley A, Ricci F, Emmenegger M, Kosmoliaptsis V, Theel E, Mills J, Sholukh A, Aguzzi A, Iwasaki A, Lynn A, Knowles T. Serological fingerprints link antiviral activity of therapeutic antibodies to affinity and concentration. Scientific Reports 2022, 12: 19791. PMID: 36396691, PMCID: PMC9672333, DOI: 10.1038/s41598-022-22214-z.
- Gut microbiome dysbiosis in antibiotic-treated COVID-19 patients is associated with microbial translocation and bacteremiaBernard-Raichon L, Venzon M, Klein J, Axelrad J, Zhang C, Sullivan A, Hussey G, Casanovas-Massana A, Noval M, Valero-Jimenez A, Gago J, Putzel G, Pironti A, Wilder E, Thorpe L, Littman D, Dittmann M, Stapleford K, Shopsin B, Torres V, Ko A, Iwasaki A, Cadwell K, Schluter J. Gut microbiome dysbiosis in antibiotic-treated COVID-19 patients is associated with microbial translocation and bacteremia. Nature Communications 2022, 13: 5926. PMID: 36319618, PMCID: PMC9626559, DOI: 10.1038/s41467-022-33395-6.
- The matricellular protein SPARC induces inflammatory interferon-response in macrophages during agingRyu S, Sidorov S, Ravussin E, Artyomov M, Iwasaki A, Wang A, Dixit VD. The matricellular protein SPARC induces inflammatory interferon-response in macrophages during aging. Immunity 2022, 55: 1609-1626.e7. PMID: 35963236, PMCID: PMC9474643, DOI: 10.1016/j.immuni.2022.07.007.
- Abstract 1380: Setdb1 -loss reactivates ERV expression and interferon signaling to induce immune-mediated melanoma clearanceMcGeary M, Damsky W, Daniels D, Micevic G, Song E, Lou H, Calderwood C, Paradkar S, Iwasaki A, Calderwood D, Turk B, Bosenberg M. Abstract 1380: Setdb1 -loss reactivates ERV expression and interferon signaling to induce immune-mediated melanoma clearance. Cancer Research 2022, 82: 1380-1380. DOI: 10.1158/1538-7445.am2022-1380.
- Abstract 1357: T cell memory and the critical effectors of successful anticancer immune responseDaniels A, Damsky W, McGeary M, Iwasaki A, Bosenberg M. Abstract 1357: T cell memory and the critical effectors of successful anticancer immune response. Cancer Research 2022, 82: 1357-1357. DOI: 10.1158/1538-7445.am2022-1357.
- Multiscale PHATE identifies multimodal signatures of COVID-19Kuchroo M, Huang J, Wong P, Grenier JC, Shung D, Tong A, Lucas C, Klein J, Burkhardt DB, Gigante S, Godavarthi A, Rieck B, Israelow B, Simonov M, Mao T, Oh JE, Silva J, Takahashi T, Odio CD, Casanovas-Massana A, Fournier J, Farhadian S, Dela Cruz C, Ko A, Hirn M, Wilson F, Hussin J, Wolf G, Iwasaki A, Krishnaswamy S. Multiscale PHATE identifies multimodal signatures of COVID-19. Nature Biotechnology 2022, 40: 681-691. PMID: 35228707, PMCID: PMC10015653, DOI: 10.1038/s41587-021-01186-x.
- Lack of association between pandemic chilblains and SARS-CoV-2 infectionGehlhausen JR, Little AJ, Ko CJ, Emmenegger M, Lucas C, Wong P, Klein J, Lu P, Mao T, Jaycox J, Wang E, Ugwu N, Muenker C, Mekael D, Klein R, Patrignelli R, Antaya R, McNiff J, Damsky W, Kamath K, Shon J, Ring A, Yildirim I, Omer S, Ko A, Aguzzi A, Iwasaki A, Obaid A, Lu-Culligan A, Nelson A, Brito A, Nunez A, Martin A, Watkins A, Geng B, Kalinich C, Harden C, Todeasa C, Jensen C, Kim D, McDonald D, Shepard D, Courchaine E, White E, Song E, Silva E, Kudo E, DeIuliis G, Rahming H, Park H, Matos I, Nouws J, Valdez J, Fauver J, Lim J, Rose K, Anastasio K, Brower K, Glick L, Sharma L, Sewanan L, Knaggs L, Minasyan M, Batsu M, Petrone M, Kuang M, Nakahata M, Campbell M, Linehan M, Askenase M, Simonov M, Smolgovsky M, Sonnert N, Naushad N, Vijayakumar P, Martinello R, Datta R, Handoko R, Bermejo S, Prophet S, Bickerton S, Velazquez S, Alpert T, Rice T, Khoury-Hanold W, Peng X, Yang Y, Cao Y, Strong Y. Lack of association between pandemic chilblains and SARS-CoV-2 infection. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2122090119. PMID: 35217624, PMCID: PMC8892496, DOI: 10.1073/pnas.2122090119.
- Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19Unterman A, Sumida TS, Nouri N, Yan X, Zhao AY, Gasque V, Schupp JC, Asashima H, Liu Y, Cosme C, Deng W, Chen M, Raredon MSB, Hoehn KB, Wang G, Wang Z, DeIuliis G, Ravindra NG, Li N, Castaldi C, Wong P, Fournier J, Bermejo S, Sharma L, Casanovas-Massana A, Vogels CBF, Wyllie AL, Grubaugh ND, Melillo A, Meng H, Stein Y, Minasyan M, Mohanty S, Ruff WE, Cohen I, Raddassi K, Niklason L, Ko A, Montgomery R, Farhadian S, Iwasaki A, Shaw A, van Dijk D, Zhao H, Kleinstein S, Hafler D, Kaminski N, Dela Cruz C. Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19. Nature Communications 2022, 13: 440. PMID: 35064122, PMCID: PMC8782894, DOI: 10.1038/s41467-021-27716-4.
- 301. Detection of Pneumococcal Pneumonia During SARS-CoV-2 InfectionWatkins A, Yolda-Carr D, Ott I, Nakahata M, Moore A, Muenker M, Tokuyama M, Vogels C, Campbell M, Datta R, Cruz C, Farhadian S, Iwasaki A, Ko A, Grubaugh N, Alexander-Parrish R, Arguedas A, Gessner B, Weinberger D, Wyllie A. 301. Detection of Pneumococcal Pneumonia During SARS-CoV-2 Infection. Open Forum Infectious Diseases 2021, 8: s257-s257. PMCID: PMC8644655, DOI: 10.1093/ofid/ofab466.503.
- High-resolution epitope mapping and characterization of SARS-CoV-2 antibodies in large cohorts of subjects with COVID-19Haynes WA, Kamath K, Bozekowski J, Baum-Jones E, Campbell M, Casanovas-Massana A, Daugherty PS, Dela Cruz CS, Dhal A, Farhadian SF, Fitzgibbons L, Fournier J, Jhatro M, Jordan G, Klein J, Lucas C, Kessler D, Luchsinger LL, Martinez B, Catherine Muenker M, Pischel L, Reifert J, Sawyer JR, Waitz R, Wunder EA, Zhang M, Iwasaki A, Ko A, Shon J. High-resolution epitope mapping and characterization of SARS-CoV-2 antibodies in large cohorts of subjects with COVID-19. Communications Biology 2021, 4: 1317. PMID: 34811480, PMCID: PMC8608966, DOI: 10.1038/s42003-021-02835-2.
- Abstract 12518: Susceptibility of Mature Human Myocardial Cell Types to SARS-CoV-2Sotolongo A, Klein J, Pena-Hernandez M, Johnson J, Geirsson A, Pober J, Iwasaki A, Gruber P. Abstract 12518: Susceptibility of Mature Human Myocardial Cell Types to SARS-CoV-2. Circulation 2021, 144: a12518-a12518. DOI: 10.1161/circ.144.suppl_1.12518.
- A stem-loop RNA RIG-I agonist protects against acute and chronic SARS-CoV-2 infection in miceMao T, Israelow B, Lucas C, Vogels CBF, Gomez-Calvo ML, Fedorova O, Breban MI, Menasche BL, Dong H, Linehan M, Alpert T, Anderson F, Earnest R, Fauver J, Kalinich C, Munyenyembe K, Ott I, Petrone M, Rothman J, Watkins A, Wilen C, Landry M, Grubaugh N, Pyle A, Iwasaki A. A stem-loop RNA RIG-I agonist protects against acute and chronic SARS-CoV-2 infection in mice. Journal Of Experimental Medicine 2021, 219: e20211818. PMID: 34757384, PMCID: PMC8590200, DOI: 10.1084/jem.20211818.
- KDM5B promotes immune evasion by recruiting SETDB1 to silence retroelementsZhang SM, Cai WL, Liu X, Thakral D, Luo J, Chan LH, McGeary MK, Song E, Blenman KRM, Micevic G, Jessel S, Zhang Y, Yin M, Booth CJ, Jilaveanu LB, Damsky W, Sznol M, Kluger HM, Iwasaki A, Bosenberg MW, Yan Q. KDM5B promotes immune evasion by recruiting SETDB1 to silence retroelements. Nature 2021, 598: 682-687. PMID: 34671158, PMCID: PMC8555464, DOI: 10.1038/s41586-021-03994-2.
- Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunityLucas C, Vogels CBF, Yildirim I, Rothman JE, Lu P, Monteiro V, Gehlhausen JR, Campbell M, Silva J, Tabachnikova A, Peña-Hernandez MA, Muenker MC, Breban MI, Fauver JR, Mohanty S, Huang J, Shaw A, Ko A, Omer S, Grubaugh N, Iwasaki A. Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity. Nature 2021, 600: 523-529. PMID: 34634791, PMCID: PMC9348899, DOI: 10.1038/s41586-021-04085-y.
- Author Correction: Delayed production of neutralizing antibodies correlates with fatal COVID-19Lucas C, Klein J, Sundaram ME, Liu F, Wong P, Silva J, Mao T, Oh JE, Mohanty S, Huang J, Tokuyama M, Lu P, Venkataraman A, Park A, Israelow B, Vogels CBF, Muenker MC, Chang CH, Casanovas-Massana A, Moore AJ, Zell J, Fournier JB, Wyllie A, Campbell M, Lee A, Chun H, Grubaugh N, Schulz W, Farhadian S, Dela Cruz C, Ring A, Shaw A, Wisnewski A, Yildirim I, Ko A, Omer S, Iwasaki A. Author Correction: Delayed production of neutralizing antibodies correlates with fatal COVID-19. Nature Medicine 2021, 27: 1309-1309. PMID: 34145437, PMCID: PMC8212078, DOI: 10.1038/s41591-021-01416-4.
- A phase II evaluation of pembrolizumab in recurrent microsatellite instability-high (MSI-H) endometrial cancer patients with Lynch-like versus MLH-1 methylated characteristics (NCT02899793).Roque D, Bellone S, Siegel E, Buza N, Bonazzoli E, Guglielmi A, Zammataro L, Nagarkatti N, Zaidi S, Lee J, Schwartz P, Ratner E, Alexandrov L, Iwasaki A, Kong Y, Song E, Dong W, Elvin J, Choi J, Santin A. A phase II evaluation of pembrolizumab in recurrent microsatellite instability-high (MSI-H) endometrial cancer patients with Lynch-like versus MLH-1 methylated characteristics (NCT02899793). Journal Of Clinical Oncology 2021, 39: 5523-5523. DOI: 10.1200/jco.2021.39.15_suppl.5523.
- Diverse functional autoantibodies in patients with COVID-19Wang EY, Mao T, Klein J, Dai Y, Huck JD, Jaycox JR, Liu F, Zhou T, Israelow B, Wong P, Coppi A, Lucas C, Silva J, Oh JE, Song E, Perotti ES, Zheng NS, Fischer S, Campbell M, Fournier JB, Wyllie AL, Vogels CBF, Ott IM, Kalinich CC, Petrone ME, Watkins AE, Dela Cruz C, Farhadian S, Schulz W, Ma S, Grubaugh N, Ko A, Iwasaki A, Ring A. Diverse functional autoantibodies in patients with COVID-19. Nature 2021, 595: 283-288. PMID: 34010947, DOI: 10.1038/s41586-021-03631-y.
- Delayed production of neutralizing antibodies correlates with fatal COVID-19Lucas C, Klein J, Sundaram ME, Liu F, Wong P, Silva J, Mao T, Oh JE, Mohanty S, Huang J, Tokuyama M, Lu P, Venkataraman A, Park A, Israelow B, Vogels CBF, Muenker MC, Chang CH, Casanovas-Massana A, Moore AJ, Zell J, Fournier JB, Wyllie A, Campbell M, Lee A, Chun H, Grubaugh N, Schulz W, Farhadian S, Dela Cruz C, Ring A, Shaw A, Wisnewski A, Yildirim I, Ko A, Omer S, Iwasaki A. Delayed production of neutralizing antibodies correlates with fatal COVID-19. Nature Medicine 2021, 27: 1178-1186. PMID: 33953384, PMCID: PMC8785364, DOI: 10.1038/s41591-021-01355-0.
- Endogenous retroviruses mediate IFN-independent protection against vaginal HSV-2 infectionTokuyama M, Jayewickreme R, Mao T, Philbrick W, Kong Y, Dong H, Treger R, Rakib T, Iwasaki A. Endogenous retroviruses mediate IFN-independent protection against vaginal HSV-2 infection. The Journal Of Immunology 2021, 206: 20.39-20.39. DOI: 10.4049/jimmunol.206.supp.20.39.
- 68. Active Monitoring of a Healthcare Worker Cohort During the COVID-19 EpidemicDatta R, Campbell M, Wyllie A, Casanovas-Massana A, Handoko R, Sewanan L, Naushad N, Simonov M, White E, Valdez J, Liu F, Omer S, Dela Cruz C, Farhadian S, Ring A, Iwasaki A, Grubaugh N, Martinello R, Ko A. 68. Active Monitoring of a Healthcare Worker Cohort During the COVID-19 Epidemic. Open Forum Infectious Diseases 2020, 7: s165-s165. PMCID: PMC7778054, DOI: 10.1093/ofid/ofaa439.378.
- 456. Implementing an At-Home Smell Test for Early Assessment of COVID-19 in High-Risk Healthcare WorkersWeiss J, Attuquayefio T, White E, Geng B, Handoko R, Herz R, White T, Iwasaki A, Grubaugh N, Datta R, Campbell M, Martinello R, Ko A, Small D, Farhadian S. 456. Implementing an At-Home Smell Test for Early Assessment of COVID-19 in High-Risk Healthcare Workers. Open Forum Infectious Diseases 2020, 7: s295-s296. PMCID: PMC7776583, DOI: 10.1093/ofid/ofaa439.649.
- Sex differences in immune responses that underlie COVID-19 disease outcomesTakahashi T, Ellingson MK, Wong P, Israelow B, Lucas C, Klein J, Silva J, Mao T, Oh JE, Tokuyama M, Lu P, Venkataraman A, Park A, Liu F, Meir A, Sun J, Wang EY, Casanovas-Massana A, Wyllie AL, Vogels CBF, Earnest R, Lapidus S, Ott IM, Moore AJ, Shaw A, Fournier J, Odio C, Farhadian S, Dela Cruz C, Grubaugh N, Schulz W, Ring A, Ko A, Omer S, Iwasaki A. Sex differences in immune responses that underlie COVID-19 disease outcomes. Nature 2020, 588: 315-320. PMID: 32846427, PMCID: PMC7725931, DOI: 10.1038/s41586-020-2700-3.
- Longitudinal analyses reveal immunological misfiring in severe COVID-19Lucas C, Wong P, Klein J, Castro TBR, Silva J, Sundaram M, Ellingson MK, Mao T, Oh JE, Israelow B, Takahashi T, Tokuyama M, Lu P, Venkataraman A, Park A, Mohanty S, Wang H, Wyllie AL, Vogels CBF, Earnest R, Lapidus S, Ott IM, Moore AJ, Muenker MC, Fournier JB, Campbell M, Odio CD, Casanovas-Massana A, Herbst R, Shaw A, Medzhitov R, Schulz W, Grubaugh N, Dela Cruz C, Farhadian S, Ko A, Omer S, Iwasaki A. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature 2020, 584: 463-469. PMID: 32717743, PMCID: PMC7477538, DOI: 10.1038/s41586-020-2588-y.
- Experimental Evolution of Human Rhinovirus Strains Adapting to Mouse CellsWasik B, Wasik B, Foxman E, Iwasaki A, Turner P. Experimental Evolution of Human Rhinovirus Strains Adapting to Mouse Cells. 2020, 145-157. DOI: 10.1007/978-3-030-39831-6_12.
- Conventional type 2 dendritic cells and natural killer cells mediate control of early metastatic seedingWeizman O, Krykbaeva I, Bosenburg M, Iwasaki A. Conventional type 2 dendritic cells and natural killer cells mediate control of early metastatic seeding. The Journal Of Immunology 2020, 204: 88.17-88.17. DOI: 10.4049/jimmunol.204.supp.88.17.
- Chapter 43 Mucosal Vaccines for Genital HerpesOh J, Iwasaki A. Chapter 43 Mucosal Vaccines for Genital Herpes. 2020, 723-734. DOI: 10.1016/b978-0-12-811924-2.00043-2.
- Hematopoietic type I interferon signaling controls Zika virus viremia after intravaginal exposureYockey L, Jurado K, Condiff E, Iwasaki A. Hematopoietic type I interferon signaling controls Zika virus viremia after intravaginal exposure. American Journal Of Obstetrics And Gynecology 2019, 221: 675. DOI: 10.1016/j.ajog.2019.10.094.
- Loss of METTL3 Mediated m6A RNA Modification Results in Double-Stranded RNA Induced Innate Immune Response and Hematopoietic FailureGao Y, Vasic R, Song Y, Teng R, Gbyli R, Biancon G, Nelakanti R, Kudo E, Liu W, Ardasheva A, Fu X, Wang X, Joshi P, Dura B, Lee V, Viero G, Iwasaki A, Fan R, Xiao A, Flavell R, Li H, Tebaldi T, Halene S. Loss of METTL3 Mediated m6A RNA Modification Results in Double-Stranded RNA Induced Innate Immune Response and Hematopoietic Failure. Blood 2019, 134: 450-450. DOI: 10.1182/blood-2019-130442.
- Ketogenic diet activates protective γδ T cell responses against influenza virus infectionGoldberg EL, Molony RD, Kudo E, Sidorov S, Kong Y, Dixit VD, Iwasaki A. Ketogenic diet activates protective γδ T cell responses against influenza virus infection. Science Immunology 2019, 4 PMID: 31732517, PMCID: PMC7189564, DOI: 10.1126/sciimmunol.aav2026.
- Intratumoral delivery of RIG-I agonist induces robust anti-tumor immune responsesJiang X, Fedorova O, Linehan M, Dong H, Pyle A, Iwasaki A. Intratumoral delivery of RIG-I agonist induces robust anti-tumor immune responses. The Journal Of Immunology 2019, 202: 194.28-194.28. DOI: 10.4049/jimmunol.202.supp.194.28.
- Antigen presentation by CD301b+ dermal dendritic cells dictates CD4+ T cell fateTatsumi N, Iwasaki A, Kumamoto Y. Antigen presentation by CD301b+ dermal dendritic cells dictates CD4+ T cell fate. The Journal Of Immunology 2019, 202: 56.9-56.9. DOI: 10.4049/jimmunol.202.supp.56.9.
- Ketogenic diet activates protective γδ T cell responses against influenza virus infectionGoldberg E, Molony R, Sidorov S, Kudo E, Dixit V, Iwasaki A. Ketogenic diet activates protective γδ T cell responses against influenza virus infection. The Journal Of Immunology 2019, 202: 62.7-62.7. DOI: 10.4049/jimmunol.202.supp.62.7.
- 111 Role of platelets in the differentiation of monocytes into dendritic cell-like antigen presenting cellsHan P, Hanlon D, Filler R, Robinson E, Zhang K, Fan R, Iwasaki A, Fahmy T, Edelson R. 111 Role of platelets in the differentiation of monocytes into dendritic cell-like antigen presenting cells. Journal Of Investigative Dermatology 2018, 138: s19. DOI: 10.1016/j.jid.2018.03.115.
- 1 Type I Interferon Is Necessary and Sufficient for Alloimmunization to Transfused KEL-Expressing RBCs in MiceGibb D, Liu J, Natarajan P, Santhanakrishnan M, Madrid D, Eisenbarth S, Zimring J, Iwasaki A, Hendrickson J. 1 Type I Interferon Is Necessary and Sufficient for Alloimmunization to Transfused KEL-Expressing RBCs in Mice. American Journal Of Clinical Pathology 2018, 149: s163-s163. DOI: 10.1093/ajcp/aqx149.370.
- Publisher Correction: Antiviral CD8 T cells induce Zika-virus-associated paralysis in miceJurado K, Yockey L, Wong P, Lee S, Huttner A, Iwasaki A. Publisher Correction: Antiviral CD8 T cells induce Zika-virus-associated paralysis in mice. Nature Microbiology 2018, 3: 255-255. DOI: 10.1038/s41564-017-0101-7.
- β-hydroxybutyrate deactivates neutrophil NLRP3 inflammasome to relieve gout flaresGoldberg E, Asher J, Molony R, Shaw A, Zeiss C, Wang C, Morozova-Roche L, Herzog R, Iwasaki A, Dixit V. β-hydroxybutyrate deactivates neutrophil NLRP3 inflammasome to relieve gout flares. The Journal Of Immunology 2017, 198: 206.18-206.18. DOI: 10.4049/jimmunol.198.supp.206.18.
- β-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout FlaresGoldberg EL, Asher JL, Molony RD, Shaw AC, Zeiss CJ, Wang C, Morozova-Roche LA, Herzog RI, Iwasaki A, Dixit VD. β-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares. Cell Reports 2017, 18: 2077-2087. PMID: 28249154, PMCID: PMC5527297, DOI: 10.1016/j.celrep.2017.02.004.
- Type 1 Interferon Regulates Inflammation Associated RBC Alloimmunization By Promoting Monocyte-Derived Dendritic Cell Erythrophagocytosis in MiceGibb D, Natarajan P, Liu J, Santhanakrishnan M, Iwasaki A, Hendrickson J. Type 1 Interferon Regulates Inflammation Associated RBC Alloimmunization By Promoting Monocyte-Derived Dendritic Cell Erythrophagocytosis in Mice. Blood 2016, 128: 19-19. DOI: 10.1182/blood.v128.22.19.19.
- 741 Identification of a specific subset of monocytes/macrophages that coordinates skin wound healingShook B, Iwasaki A, Horsley V. 741 Identification of a specific subset of monocytes/macrophages that coordinates skin wound healing. Journal Of Investigative Dermatology 2016, 136: s131. DOI: 10.1016/j.jid.2016.02.784.
- Chapter 25 Mucosal Dendritic Cells Origins, Subsets, and BiologyLambrecht B, Iwasaki A, Kelsall B. Chapter 25 Mucosal Dendritic Cells Origins, Subsets, and Biology. 2015, 489-541. DOI: 10.1016/b978-0-12-415847-4.00025-2.
- Innate immunityIwasaki A, Peiris M. Innate immunity. 2013, 267-282. DOI: 10.1002/9781118636817.ch17.
- Innate Immunity to VirusesIwasaki A. Innate Immunity to Viruses. 2010, 183-196. DOI: 10.1128/9781555816872.ch15.
- Cholera toxin inhibits IL-12 production and CD8α+ dendritic cell differentiation by cAMP-mediated inhibition of IRF8 functionla Sala A, He J, Laricchia-Robbio L, Gorini S, Iwasaki A, Braun M, Yap G, Sher A, Ozato K, Kelsall B. Cholera toxin inhibits IL-12 production and CD8α+ dendritic cell differentiation by cAMP-mediated inhibition of IRF8 function. Journal Of Experimental Medicine 2009, 206: 1635-1635. PMCID: PMC2715084, DOI: 10.1084/jem.2008091262209c.
- Innate Recognition of Viral Infection and the Involvement of AutophagyRamanathan B, Iwasaki A. Innate Recognition of Viral Infection and the Involvement of Autophagy. 2009, 209-228. DOI: 10.1142/9789812833808_0009.
- In vivo requirement for autophagy in antigen presentation by dendritic cellsLEE H, Lee Y, Chervonsky A, Mizushima N, Iwasaki A. In vivo requirement for autophagy in antigen presentation by dendritic cells. The FASEB Journal 2008, 22: 1068.13-1068.13. DOI: 10.1096/fasebj.22.1_supplement.1068.13.
- Epithelial dendritic cells in vagina rapidly renew from bone marrow precursorsIijima N, Linehan M, Saeland S, Iwasaki A. Epithelial dendritic cells in vagina rapidly renew from bone marrow precursors. The FASEB Journal 2008, 22: 851.7-851.7. DOI: 10.1096/fasebj.22.1_supplement.851.7.
- T helper dependent CTL migration into the vaginal mucosaNakanishi Y, Lu B, Gerard C, Iwasaki A. T helper dependent CTL migration into the vaginal mucosa. The FASEB Journal 2008, 22: 852.5-852.5. DOI: 10.1096/fasebj.22.1_supplement.852.5.
- The Use of Bone Marrow-Chimeric Mice in Elucidating Immune MechanismsIwasaki A. The Use of Bone Marrow-Chimeric Mice in Elucidating Immune Mechanisms. 2006, 127: 281-292. DOI: 10.1385/1-59745-168-1:281.
- CCL9 Is Secreted by the Follicle-Associated Epithelium and Recruits Dome Region Peyer’s Patch CD11b+ Dendritic CellsZhao X, Sato A, Dela Cruz C, Linehan M, Luegering A, Kucharzik T, Shirakawa A, Marquez G, Farber J, Williams I, Iwasaki A. CCL9 Is Secreted by the Follicle-Associated Epithelium and Recruits Dome Region Peyer’s Patch CD11b+ Dendritic Cells. The Journal Of Immunology 2004, 172: 7220-7220. DOI: 10.4049/jimmunol.172.11.7220-a.
- The role of dendritic cells in the induction of oral tolerance and immunityFLEETON M, IWASAKI A, CONTRACTOR N, LEON F, HE J, WETZEL D, DERMODY T, KELSALL B. The role of dendritic cells in the induction of oral tolerance and immunity. Immunological Medicine 2003, 26: 200-200. DOI: 10.2177/jsci.26.200.
- Unique Functions of CD11b+, CD8α+, and Double-Negative Peyer’s Patch Dendritic CellsIwasaki A, Kelsall B. Unique Functions of CD11b+, CD8α+, and Double-Negative Peyer’s Patch Dendritic Cells. The Journal Of Immunology 2001, 166: 4884-4890. PMID: 11290765, DOI: 10.4049/jimmunol.166.8.4884.
- Requirements for the Maintenance of Th1 Immunity In Vivo Following DNA Vaccination: A Potential Immunoregulatory Role for CD8+ T CellsGurunathan S, Stobie L, Prussin C, Sacks D, Glaichenhaus N, Iwasaki A, Fowell D, Locksley R, Chang J, Wu C, Seder R. Requirements for the Maintenance of Th1 Immunity In Vivo Following DNA Vaccination: A Potential Immunoregulatory Role for CD8+ T Cells. The Journal Of Immunology 2000, 165: 915-924. PMID: 10878366, DOI: 10.4049/jimmunol.165.2.915.
- Primary Role for GI Protein Signaling in the Regulation of Interleukin 12 Production and the Induction of T Helper Cell Type 1 ResponsesHe J, Gurunathan S, Iwasaki A, Ash-Shaheed B, Kelsall B. Primary Role for GI Protein Signaling in the Regulation of Interleukin 12 Production and the Induction of T Helper Cell Type 1 Responses. Journal Of Experimental Medicine 2000, 191: 1605-1610. PMID: 10790434, PMCID: PMC2213427, DOI: 10.1084/jem.191.9.1605.
- Localization of Distinct Peyer's Patch Dendritic Cell Subsets and Their Recruitment by Chemokines Macrophage Inflammatory Protein (Mip)-3α, Mip-3β, and Secondary Lymphoid Organ ChemokineIwasaki A, Kelsall B. Localization of Distinct Peyer's Patch Dendritic Cell Subsets and Their Recruitment by Chemokines Macrophage Inflammatory Protein (Mip)-3α, Mip-3β, and Secondary Lymphoid Organ Chemokine. Journal Of Experimental Medicine 2000, 191: 1381-1394. PMID: 10770804, PMCID: PMC2193144, DOI: 10.1084/jem.191.8.1381.
- Freshly Isolated Peyer's Patch, but Not Spleen, Dendritic Cells Produce Interleukin 10 and Induce the Differentiation of T Helper Type 2 CellsIwasaki A, Kelsall B. Freshly Isolated Peyer's Patch, but Not Spleen, Dendritic Cells Produce Interleukin 10 and Induce the Differentiation of T Helper Type 2 Cells. Journal Of Experimental Medicine 1999, 190: 229-240. PMID: 10432286, PMCID: PMC2195574, DOI: 10.1084/jem.190.2.229.
- I. Mucosal dendritic cells: their specialized role in initiating T cell responses*Iwasaki A, Kelsall B. I. Mucosal dendritic cells: their specialized role in initiating T cell responses*. American Journal Of Physiology 1999, 276: g1074-g1078. PMID: 10329996, DOI: 10.1152/ajpgi.1999.276.5.g1074.
Clinical Trials
Conditions | Study Title |
---|---|
COVID-19 Inpatient; COVID-19 Outpatient | Long Covid: Understanding Immune, Symptom, and Treatment Experiences Nationwide (LISTEN Study) |