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.