IL-10 inhibits neuraminidase-activated TGF-β and facilitates Th1 phenotype during early phase of infection.
Th1 cells control their activity by producing regulatory IL-10. Here we report that Th1 cell-derived IL-10 facilitates their expansion and, in addition, augments Th1 cell production of IFN-γ, TNF-α and IL-2 during the early phase of influenza. In our antigen-specific mouse experimental system, influenza haemagglutinin-specific CD4(+) T cells respond to infection with the induction of T-bet, and produce both IFN-γ and IL-10. In the early phase of infection, an abundance of viral neuraminidase causes TGF-β activation of haemagglutinin-specific CD4(+) T cells. CD4(+) T-cell-derived IL-10 inhibits neuraminidase-driven TGF-β activation and counteracts the virus-mediated immune suppression. As the host eradicates the virus, neuraminidase activity wanes and IL-10 receptors are upregulated on CD4(+) T cells in the late phase of infection. IL-10 then suppresses immune activation and aids in recovery from infection and inflammation. These results reveal a previously unrecognized function of Th1 cell-derived IL-10 in vivo.
Division of Infectious Diseases, Department of Medicine, Chang Gung Memorial Hospital, Chang Gung University, Kweishan, Taoyuan 33333, Taiwan.
Avijit
A
Dutta
Division of Infectious Diseases, Department of Medicine, Chang Gung Memorial Hospital, Chang Gung University, Kweishan, Taoyuan 33333, Taiwan.
Ching-Tai
CT
Huang
Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University, Kweishan, Taoyuan 33333, Taiwan.
Tse-Ching
TC
Chen
Division of Hepatogastroenterology, Department of Medicine, Chang Gung Memorial Hospital, Chang Gung University, Kweishan, Taoyuan 33333, Taiwan.
Chun-Yen
CY
Lin
Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University, Kweishan, Taoyuan 33333, Taiwan.
Cheng-Hsun
CH
Chiu
Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Chang Gung University, Kweishan, Taoyuan 33333, Taiwan.
Yung-Chang
YC
Lin
Division of Infectious Diseases, Department of Medicine, Chang Gung Memorial Hospital, Chang Gung University, Kweishan, Taoyuan 33333, Taiwan.
Chia-Shiang
CS
Chang
Division of Infectious Diseases, Department of Medicine, Chang Gung Memorial Hospital, Chang Gung University, Kweishan, Taoyuan 33333, Taiwan.
Yueh-Chia
YC
He
D019264:Adoptive Transfer; D000818:Animals; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology*; D007376:Interleukin-2 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009439:Neuraminidase / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D009439:Neuraminidase