Interleukin-4 and interleukin-10 are involved in host resistance to Staphylococcus aureus infection through regulation of gamma interferon.
Our previous study showed that gamma interferon (IFN-gamma), a T-helper 1 (Th1)-type cytokine, plays a detrimental role in Staphylococcus aureus infection in mice. In this study, the role of Th2-type cytokines such as interleukin-4 (IL-4) and IL-10 in S. aureus infection was investigated. IL-10 mRNA was induced in parallel with IFN-gamma 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-gamma 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-gamma 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-gamma in S. aureus infection in IFN-gamma(-/-) 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-gamma(-/-) mice compared with those in IFN-gamma(+/+) mice. Administration of MAb against IL-4 or IL-10 failed to affect bacterial growth in the spleens and kidneys of IFN-gamma(-/-) mice irrespective of the expression of Th2 response. These results suggest that S. aureus infection induced a Th2 response and that IL-4 and IL-10 might play a protective role through the regulation of IFN-gamma in S. aureus infection.
Sasaki
S
S
Department of Bacteriology, Hirosaki University School of Medicine, Hirosaki, Japan.
Nishikawa
S
S
Miura
T
T
Mizuki
M
M
Yamada
K
K
Madarame
H
H
Tagawa
Y I
YI
Iwakura
Y
Y
Nakane
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D002478:Cells, Cultured; D015870:Gene Expression; D007113:Immunity, Innate / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger; D013154:Spleen / Q000166:cytology; D013203:Staphylococcal Infections / Q000276:immunology* / Q000473:pathology
D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma