Fig. 4
From: Aging and respiratory viral infection: from acute morbidity to chronic sequelae
Aging is associated with the development of pulmonary sequelae following respiratory virus clearance. Acute respiratory viral infection can lead to persistence of inflammatory, pathological and pro-fibrotic responses in the aged lung. Active virus RNA remnants could promote non-resolving inflammation. Loss of PPAR-γ function in macrophages could also contribute to the persistent lung fibrotic sequelae. Extensive accumulation of TRM cells in aged lungs fail to provide protective anti-viral response upon secondary challenge. Instead, these TRM cells could induce bystander tissue inflammation and pathology, which drive the development of non-resolving inflammatory and fibrotic sequelae. Dysfunctional Treg could contribute to the loss of regulation in pro-fibrotic responses through CD4-TRM-dependent manner. Another CD4 population, which was reported to produce pro-inflammatory cytokines, was found in the BAL of COVID-19 patients and termed Trm17. Trm17 is also considered to interact with pro-fibrotic macrophages and thus contribute the pro-fibrotic response in the lung. Other potential candidates that could be involved in the development of chronic sequelae following acute virus infection include cells that are involved in the TH2 response and cells that undergo cellular senescence