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Molecular Medicine

, Volume 20, Issue 1, pp 109–119 | Cite as

Interleukin-22 Promotes T Helper 1 (Th1)/Th17 Immunity in Chlamydial Lung Infection

  • Ying Peng
  • Xiaoling Gao
  • Jie Yang
  • Sudhanshu Shekhar
  • Shuhe Wang
  • Yijun Fan
  • Weiming Zhao
  • Xi Yang
Research Article

Abstract

The role of interleukin-22 (IL-22) in intracellular bacterial infections is a controversial issue, although the contribution of this cytokine to host defense against extracellular bacterial pathogens has been well established. In this study, we focused on an intracellular bacterium, Chlamydia, and evaluated the production and function of IL-22 in host defense against chlamydial lung infection using a mouse model. We found that Chlamydia muridarum infection elicited quick IL-22 responses in the lung, which increased during infection and were reduced when bacterial loads decreased. More importantly, blockade of endogenous IL-22 using neutralizing anti-IL-22 monoclonal antibodies (mAb) resulted in more severe disease in the mice, leading to significantly higher weight loss and bacterial growth and much more severe pathological changes than treatment with isotype control antibody. Immunological analyses identified significantly lower T helper 1 (Th1) and Th17 responses in the IL-22-neutralized mice. In contrast, intranasal administration of exogenous IL-22 significantly enhanced protection following chlamydial lung infection, which was associated with a significant increase of Th17 response. The data demonstrate that IL-22 is a critical cytokine, mediating host defense against chlamydial lung infection and coordinating the function of distinct Th-cell subsets, particularly Th1 and Th17, in the process.

Notes

Acknowledgments

This work was supported by grants from the Canadian Institutes of Health Research to X Yang (CCI92213 and CIHR/RPA-124955) and grants from the National Natural Sciences Foundation of China (#30811120425 and #81271853) to W Zhao. Y Peng was a recipient of a PhD Studentship for Overseas Study from Shandong University.

Supplementary material

10020_2014_2001109_MOESM1_ESM.pdf (557 kb)
Supplementary material, approximately 556 KB.

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Authors and Affiliations

  • Ying Peng
    • 1
    • 2
  • Xiaoling Gao
    • 1
  • Jie Yang
    • 1
  • Sudhanshu Shekhar
    • 1
  • Shuhe Wang
    • 1
  • Yijun Fan
    • 1
  • Weiming Zhao
    • 2
  • Xi Yang
    • 1
    • 3
  1. 1.Departments of Medical Microbiology and ImmunologyUniversity of ManitobaWinnipegCanada
  2. 2.Department of Medical MicrobiologyShandong University School of MedicineJinan, ShandongPR China
  3. 3.Laboratory for Infection and Immunity, Departments of Medical Microbiology and ImmunologyUniversity of ManitobaWinnipegCanada

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