Robust antigen specific th17 t cell response to group a streptococcus is dependent on il-6 and intranasal route of infection

Thamotharampillai Dileepan, Jonathan L. Linehan, James J. Moon, Marion Pepper, Marc K. Jenkins, Patrick P. Cleary

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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-A b MHCII molecule. Following intranasal inoculation with GAS-2W, antigen-experienced 2W:I-A b-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-A b+ CD4 + T cells. The acquisition of IL-17A production by 2W:I-A b-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-A b-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.

Original languageEnglish (US)
Article numbere1002252
JournalPLoS pathogens
Issue number9
StatePublished - Sep 2011


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