(The) role of IL-33 in innate and adaptive immune responses against mucosal influenza virus infection

Abstract

Influenza (flu) is an acute infectious respiratory illness caused by influenza virus. Although there is a vaccine against flu, it has not been much efficient to adults 65 years and older. Studies for host defenses immunity mechanism against influenza virus infection are still needed. It has recently been reported that a considerable amount of IL-33 was produced in lung when mice were infected with influenza virus. The role of IL-33 was unclear, whether it promotes or exacerbates host protection. We, thus, definitely identified the role of IL-33 in host protection against influenza virus infection. First, when we experimented with IL-33^{-/-} mice, endogenous IL-33 did not affect the host defense immunity against PR8 infection. In our experiments, the secretion of IL-33 was very little in lung post the infection. Second, when we experimented with mouse model pre-administered intranasally with rIL-33, this IL-33 promoted host protection against PR8 infection. We wondered what kinds of immune cells expanded in response to rIL-33 and enhanced host protection against PR8 infection. Intranasal administrations of rIL-33 dramatically changed populations of immune cells in lung, mLN and spleen. Moreover, it promoted secretion of proinflammatory cytokines in lung. Administrations of rIL-33 promoted adaptive immune response as well. The injected rIL-33 facilitated secretion of neutralizing antibodies and recruitment of CD8^{+} T cells in lung. We wondered whether IL-33^{-/-} mice pre-treated with rIL-33 overcome PR8 infection. The mice succumbed to the infection. We wanted to further identify the role of endogenous IL-33 by using IL-33^{-/-} mice, whether endogenous IL-33 affects T cell responses in spleen. Endogenous IL-33 was not associated with expansion of CD8^{+} T cells, CD4^{+} T cell subsets in spleen. To summarize, the injected rIL-33 enhances host protection, which promotes both innate and adaptive immune response against PR8 infection, but the role of endogenous IL-33 is not elucidated.