Shinsuke Nishikawa

Interleukin-4 and Interleukin-10 Are Involved in Host Resistance to Staphylococcus aureus Infection through Regulation of Gamma Interferon

ABSTRACT Our previous study showed that gamma interferon (IFN-γ), a T-helper 1 (Th1)-type cytokine, plays a detrimental role inStaphylococcus aureus infection in mice. In this study, the role of Th2-type cytokines such as interleukin-4 (IL-4) and IL-10 inS. aureus infection was investigated. IL-10 mRNA was induced in parallel with IFN-γ in the spleens and kidneys of mice during S. aureus infection, whereas IL-4 mRNA was induced in the spleens but not in the kidneys of these animals. Spleen cells obtained from S. aureus-infected mice produced lower titers of IFN-γ and higher titers of IL-4 and IL-10 in response to heat-killed S. aureus than did those from uninfected mice. Administration of anti-IL-4 monoclonal antibody (MAb) or anti-IL-10 MAb inhibited the elimination of S. aureus cells from the kidneys of mice. IFN-γ mRNA expression was enhanced in the spleens of anti-IL-4 MAb- or anti-IL-10 MAb-treated mice and also in the kidneys of anti-IL-4 MAb-treated animals. Next, we evaluated the role of IFN-γ in S. aureus infection in IFN-γ−/−mice. An increase in survival rates, a decrease in bacterial numbers in the kidneys, and an amelioration of histologic abnormalities in these organs were observed in IFN-γ−/− mice compared with those in IFN-γ+/+ mice. Administration of MAb against IL-4 or IL-10 failed to affect bacterial growth in the spleens and kidneys of IFN-γ−/− mice irrespective of the expression of Th2 response. These results suggest that S. aureusinfection induced a Th2 response and that IL-4 and IL-10 might play a protective role through the regulation of IFN-γ in S. aureus infection.

Systemic Dissemination by Intrarectal Infection with Listeria monocytogenes in Mice

Orally ingested Listeria monocytogenes is known to penetrate into Peyers patches (PP) and translocate to the spleen and liver. Herein, extraintestinal dissemination of the bacterium independent of PP was investigated. Dissemination of Listeriae to the spleen and liver was observed in intrarectally infected mice as well as in intragastrically infected animals in spite that no Listeriae were detected in the small intestines of mice infected intrarectally. Decreased numbers of intestinal intraepithelial lymphocytes (iIEL) and increased numbers of lymphocytes in the contents of the small and large intestines were observed after intragastric infection and in the large intestine after intrarectal infection, giving the assumption that the leakage of iIEL caused by injury of epithelial layers in intestines might occur during infection. These results suggest that L. monocytogenes might be able to disseminate through small and large intestines in part by a PP‐independent mechanism.