Robust Antigen Specific Th17 T Cell Response to Group A Streptococcus Is Dependent on IL-6 and Intranasal Route of Infection

PLoS Pathogens

Patrick P. Cleary¹  Thamotharampillai Dileepan¹  Marc K. Jenkins²  Marion Pepper²  Jonathan L. Linehan²  James J. Moon³ 

[1] Department of Microbiology, University of Minnesota, Minneapolis, Minnesota, United States of America;Department of Microbiology-Center for Immunology, Medical School, University of Minnesota, Minneapolis, Minnesota, United States of America;The Center for Immunology & Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Cambridge, Massachusetts, United States of America

关键词: T cells;    Streptococcal infections;    Spleen;    Cytokines;    Mouse models;    Group A streptococcal infection;    Bacterial pathogens;    Blood;   

DOI  :  10.1371/journal.ppat.1002252

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Group A streptococcus (GAS, Streptococcus pyogenes) is the cause of a variety of clinical conditions, ranging from pharyngitis to autoimmune disease. Peptide-major histocompatibility complex class II (pMHCII) tetramers have recently emerged as a highly sensitive means to quantify pMHCII-specific CD4+ helper T cells and evaluate their contribution to both protective immunity and autoimmune complications induced by specific bacterial pathogens. In lieu of identifying an immunodominant peptide expressed by GAS, a surrogate peptide (2W) was fused to the highly expressed M1 protein on the surface of GAS to allow in-depth analysis of the CD4+ helper T cell response in C57BL/6 mice that express the I-Ab MHCII molecule. Following intranasal inoculation with GAS-2W, antigen-experienced 2W:I-Ab-specific CD4+ T cells were identified in the nasal-associated lymphoid tissue (NALT) that produced IL-17A or IL-17A and IFN-γ if infection was recurrent. The dominant Th17 response was also dependent on the intranasal route of inoculation; intravenous or subcutaneous inoculations produced primarily IFN-γ+ 2W:I-Ab+ CD4+ T cells. The acquisition of IL-17A production by 2W:I-Ab-specific T cells and the capacity of mice to survive infection depended on the innate cytokine IL-6. IL-6-deficient mice that survived infection became long-term carriers despite the presence of abundant IFN-γ-producing 2W:I-Ab-specific CD4+ T cells. Our results suggest that an imbalance between IL-17- and IFN-γ-producing CD4+ T cells could contribute to GAS carriage in humans.

【 授权许可】

CC BY