The Role of Innate Leukocytes during Influenza Virus Infection

Figure 2

Schematic representation of monocyte-, macrophage-, and dendritic cell- (DC-) controlled immunoprotection and immunopathology during influenza virus infection. Influenza A virus- (IAV-) infected airway epithelium produces monocyte chemoattractants: CCL2, CCL3, and CCL5. Monocytes interact with endothelium through β1 integrin, VCAM-1, and β2 integrin, ICAM-1, binding, and subsequent entry into the lung tissue is assisted by JAM. These activated monocytes secrete inflammatory cytokines that inhibit IAV replication. Monocytes exert anti-IAV activity by differentiating into phagocytic cells like macrophages and DCs. IAV infection downregulates CD200-CD200R activating macrophages. These activated macrophages release an array of inflammatory cytokines that limit IAV replication. Both conventional and plasmacytoid DCs (cDCs and pDCs) exert anti-IAV activity in lungs. IAV-activated cDCs migrate to lymph node and present antigen to CD8⁺ T cells. Chemokines, CCL12 and CCL17, secreted by infected airway epithelium provide signals for the activated cytotoxic T cells trafficking into the lungs where they lyse IAV-infected cells. The other DC subset, pDC migrate to lymph node and stimulate B cell differentiation into antibody secreting plasma cells. These antibodies neutralize IAV particles conferring humoral protection.