A Detrimental Effect of Interleukin-10 on Protective Pulmonary Humoral Immunity during Primary Influenza A Virus Infection

Abstract

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 Fc␥R 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.

Herpes simplex virus-1 evasion of CD8+ T cell accumulation contributes to viral encephalitis

“…In support of this, HSV-1 infection has been shown to induce CXCL9 expression, as shown here and in earlier studies (43). Collectively, these observations suggested that CXCL9 played opposing roles in HSV-1 virulence in the CNS, probably depending on the quantity and/or timing of CXCL9 expression during the infection, just like other cytokines such as IL-10 do in other viral infections (44,45). Therefore, HSV-1 needs to tightly regulate CXCL9 expression, and thus has evolved to express UL13 as regulator of CXCL9.…”

Memory CD4+ T cells protect against influenza through multiple synergizing mechanisms

“…Using a similar model, another study concluded that memory CD4 + T cell protection is dependent on IFN-γ and that the protective capacity of these cells remains robust in lymphocyte-deficient hosts (12). However, this study was largely restricted to monitoring the first week of infection, and the importance of IFN-γ in protection against IAV remains controversial, with diverse reports citing either no role (2,(13)(14)(15)(16)(17) or a critical contribution (17)(18)(19).…”

IL-10 inhibits neuraminidase-activated TGF-β and facilitates Th1 phenotype during early phase of infection

“…In experimental mice, IL-10 seems to aggravate the disease. IL-10 knockout (KO) mice survive better than wild-type (WT) mice upon infection with influenza virus 21,22 . However, IL-10 receptor (IL-10R) blockade after 3 days of infection increases mortality with aggravated pulmonary inflammation in mice 19 .…”