IL-10 Regulates Viral Lung Immunopathology during Acute Respiratory Syncytial Virus Infection in Mice

Abstract

Interleukin (IL-) 10 is a pleiotropic cytokine with broad immunosuppressive functions, particularly at mucosal sites such as the intestine and lung. Here we demonstrate that infection of BALB/c mice with respiratory syncytial virus (RSV) induced IL-10 production by CD4+ and CD8+ T cells in the airways at later time points (e.g. day 8); a proportion of these cells also co-produced IFN-γ. Furthermore, RSV infection of IL-10−/− mice resulted in more severe disease with enhanced weight loss, delayed recovery and greater cell infiltration of the respiratory tract without affecting viral load. In addition, IL-10−/− mice had a pronounced airway neutrophilia and heightened levels of pro-inflammatory cytokines and chemokines in the bronchoalveolar lavage fluid. Notably, the proportion of lung T cells producing IFN-γ was enhanced, suggesting that IL-10 may act in an autocrine manner to dampen effector T cell responses. Similar findings were made in mice treated with anti-IL-10R antibody and infected with RSV. Therefore, IL-10 inhibits disease and inflammation in mice infected with RSV, especially during recovery from infection.

Respiratory Syncytial Virus and Recurrent Wheeze in Healthy Preterm Infants

“…Studies in mice and humans have suggested that local production of interleukin-10 during RSV infection is a key mechanism in the development of recurrent wheeze and airway hyperresponsiveness, although mechanisms independent of interleukin-10 have also been described. 19,[33][34][35][36] We believe that alterations to the pulmonary environment and immunologic phenotype caused by RSV infection in early life eventually lead to long-term remodeling of the pulmonary system and hyperresponsiveness to respiratory viruses and nonspecific stimuli.…”

PC61 (Anti-CD25) Treatment Inhibits Influenza A Virus-Expanded Regulatory T Cells and Severe Lung Pathology during a Subsequent Heterologous Lymphocytic Choriomeningitis Virus Infection

“…These studies support the concept that the presence of Treg cells results in attenuation of effector T-cell activation. In IAV-immune mice prior to and throughout the subsequent LCMV infection, we found significantly increased numbers of IAV-expanded Treg cells and the suppressive cytokine IL-10, which has been shown to decrease pathology (19,59,60) or contribute to induction of chronic infection with high-dose LCMV clone 13 by induction of CD8 ϩ T-cell exhaustion (61-63). Thus, it was possible that depletion of Treg cell function prior to LCMV infection further increased the severity of lung pathology upon LCMV infection in IAV-immune mice.…”

Prophylaxis with a Respiratory Syncytial Virus (RSV) Anti-G Protein Monoclonal Antibody Shifts the Adaptive Immune Response to RSV rA2-line19F Infection from Th2 to Th1 in BALB/c Mice

“…RSV has been noted to affect a number of immune responses, including impairment of lymphoproliferation (69), decreased CD8 ϩ T cell response by human peripheral blood mononuclear cells (PBMCs) when infected in vitro (70), increased apoptosis of peripheral lymphocytes during acute infection in infants (71), increase in IL-10 and regulatory T cells in lungs of infected mice (72)(73)(74)(75), and altered dendritic cell stimulation of T cells in mice (76,77) and in human PBMCs or cord blood mononuclear cells in vitro (78)(79)(80). The G protein specifically has been associated with suppressing a number of immune responses, including induction of Toll-like receptor 3 (TLR3) or 4, IFN-␤ (81), proinflammatory responses of lung epithelial cells (82), lymphoproliferation (83), and activation of dendritic cells (84,85).…”