The Mucosal Immune Response to Respiratory Viruses

Because of its air-exchange function, the lung is continuously exposed to foreign particles such as microbes. Viral infections such as influenza A virus, respiratory syncytial virus, human metapneumovirus, and rhinovirus are common and the lung is a very vulnerable organ that needs to preserve gas exchange during antiviral defense. To recognize these threats and at the same time maintain tissue homeostasis, the lung is equipped with an elaborate network of innate and adaptive immune cells. The innate mucosal immune response to respiratory viruses is made up of natural killer cells and B cells producing low-affinity natural antibodies. Dendritic cells are the sentinels of the immune system linking sensing by ancient innate immune system receptors to activation of adaptive immunity to respiratory viruses. These cells also induce the polarization of virus-specific CD4 and CD8 T cell responses, necessary for viral clearance. Memory responses to viral antigens are found in the CD4 and CD8 compartment of T cells, and these cells often home back to the lung mucosa to become tissue-resident memory cells, which produce copious amounts of cytokines upon renewed viral encounter. Following respiratory viral infection, there frequently is induction of tertiary lymphoid organs such as bronchus-associated lymphoid tissues that similarly play important roles in maintaining antiviral immunity.