Regulating the adaptive immune response to respiratory virus infection

Abstract

The respiratory tract is a major portal of entry for viruses into the body. Infection of the respiratory tract can, if severe, induce life-threatening damage to the lungs. Various strategies to control virus replication and to limit immune-mediated inflammation and tissue injury have evolved in the respiratory tract. Multiple innate immune cell types, particularly dendritic cells (DCs), within the pulmonary interstitium and between airway epithelial cells are strategically poised to recognize and sample airway particulates, such as viruses. In response to respiratory virus infection, several distinct DC subsets are stimulated to migrate from the site of infection in the lungs to the draining lymph nodes. Here, these migrant DCs have a crucial role in initiating the antivirus adaptive immune response to the invading viruses. After entering the infected lungs, effector T cells that were generated in the lymph nodes undergo further modifications that are shaped by the inflammatory milieu. Co-stimulatory receptor–ligand interactions between effector T cells and various cell types presenting viral antigens in the infected lungs modulate the host adaptive immune response in situ. Effector T cells that produce pro-inflammatory mediators are also the major producers of regulatory (anti-inflammatory) cytokines, providing a fine-tuning mechanism of self-control by effector T cells responding to viruses in the inflamed tissue. The immune mechanisms that control virus replication and/or excessive inflammation in the virus-infected lungs can also predispose the individual recovering from a virus infection to bacterial superinfection. Therapeutic strategies should consider balancing the need to inhibit virus replication and excessive inflammation with the need to optimize the antibacterial functions of innate immune phagocytes, which are crucial for clearing the bacteria from the lungs.