Antigen-specific CD4+ T cell derived IL-10 is uniquely pro-inflammatory in the context of acute influenza (P6234)

Abstract

Abstract IL-10 is regarded as an anti-inflammatory cytokine which prevents damage from immunopathology with exacerbated immune responses. However, severe lung inflammation in fatal human influenza is accompanied with increased levels of IL-10 as well as other pro-inflammatory cytokines. This information raises questions regarding the role IL-10 plays in inflammation associated with acute influenza. We found that IL-10 was produced by CD4+ T cells in synchronization with pro-inflammatory cytokines during an acute influenza virus infection in mice. IL-10 supplementation during the acute phase increased inflammation leading to death, while IL-10 knockout mice displayed decreased lung inflammation and survival benefits. In the absence of IL-10, influenza-specific CD4+ T cells divided less and produced less pro-inflammatory cytokines despite unaffected Th1 polarity, no increase of regulatory T cell populations, and no alteration in the kinetics of viral eradication. Influenza-specific CD4+ T cell derived IL-10 was more important than IL-10 from other sources for the detrimental effect. In this context of acute influenza in mice, IL-10 also impeded the release of mature TGF-β with decreased neuraminidase-mediated desialylation of host immune cells. The abundance of neuraminidase may contribute to the pro-inflammatory role of IL-10 we demonstrated in this context of acute influenza virus infection.