DW: A detrimental effect of interleukin-10 on protective pulmonary humoral immunity during primary influenza A virus infection

Interleukin-10 (IL-10) is an important anti-inflammatory molecule that can cause immunosuppression and long-term pathogen persistence during chronic infection of mice with viruses such as lymphocytic choriome-ningitis virus. However, its specific role in immunity to acute viral infections is not fully understood. We found that IL-10 plays a detrimental role in host responses to acute influenza A virus since IL-10/ mice had improved viral clearance and survival after infection compared to wild-type mice. Enhanced viral clearance in IL-10/ mice was not correlated with increased CD4 or CD8 T-cell recruitment into the lung but was correlated with increased pulmonary anti-influenza virus antibody titers, and this was dependent upon the presence of T cells, primarily CD4 T cells. In addition, virus-specific antibody produced during the early stages of infection in the respiratory tract of IL-10/ but not wild-type mice was sufficient to mediate passive protection against viral challenge of naïve mice. Complement was necessary for this antibody-mediated passive protection, but FcR or neutrophil deficiency did not significantly influence viral clearance. Our results show that an absence of IL-10 at the time of primary infection leads to enhanced local virus-specific antibody production and, thus, increased protection against influenza A virus infection. Interleukin-10 (IL-10) is known to play a critical immuno-regulatory role during immune responses to microbial patho