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 choriomeningitis 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 FcgammaR 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.
Sun
Keer
K
Center for Immunology and Microbial Disease, MC-151, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USA.
Torres
Luisa
L
Metzger
Dennis W
DW
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D016753:Interleukin-10 / Q000172:deficiency / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000821:virology*; D016019:Survival Analysis; D019562:Viral Load
D000914:Antibodies, Viral; D016753:Interleukin-10