Helicobacter pylori-derived heat shock protein 60 increases the induction of regulatory T-cells associated with persistent infection

Wei-Tung Hsu; Shu-Yi Ho; Ting-Yan Jian; Han-Ning Huang; Yu-Ling Lin; Chia-Hung Chen; Tsung-Han Lin; Ming-Shiang Wu; Chang-Jer Wu; Yi-Lin Chan; Kuang-Wen Liao

doi:10.1016/j.micpath.2018.04.016

Helicobacter pylori-derived heat shock protein 60 increases the induction of regulatory T-cells associated with persistent infection

Microb Pathog. 2018 Jun:119:152-161. doi: 10.1016/j.micpath.2018.04.016. Epub 2018 Apr 13.

Authors

Affiliations

¹ Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu, Taiwan, ROC.
² Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan, ROC.
³ Department of Food Science and Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung, Taiwan, ROC.
⁴ Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan, ROC; Center for Bioinformatics Research, National Chiao Tung University, Hsinchu, Taiwan, ROC.
⁵ Department of Internal Medicine, College of Medicine, National Taiwan University Hospital, Taipei, Taiwan, ROC.
⁶ Department of Food Science and Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung, Taiwan, ROC; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan, ROC; Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan, ROC; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
⁷ Department of Life Science, Chinese Culture University, Taipei, Taiwan, ROC.
⁸ Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu, Taiwan, ROC; Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan, ROC; College of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan, ROC; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC. Electronic address: liaonms@mail.nctu.edu.tw.

PMID: 29660522
DOI: 10.1016/j.micpath.2018.04.016

Abstract

Local Treg responses are involved in Helicobacter pylori-related inflammation and clinical outcomes after infection, and H. pylori-derived HSP60 (HpHSP60) is an important virulence factor associated with gastric carcinogenesis. This study to investigate the role of HpHSP60 in immunosuppression, particularly with regard to whether it could induce the production of Treg cells. For this purpose, human peripheral blood mononuclear cells (PBMCs) were treated with or without HpHSP60 in the presence of an anti-CD3 mAb to determine the effect of HpHSP60 on cell proliferation. In this report, HpHSP60 decreased the expression of CDK4 to significantly arrest the proliferation of mitogen-stimulated T-cells, which correlated with the induction of Treg cells. Moreover, monocytic cells were essential for the induction of HpHSP60-induced Treg cells via the secretion of IL-10 and TGF-β after treatment with HpHSP60. Blockage of HpHSP60 with specific monoclonal antibodies significantly reduced the colonization of H. pylori and the expression of Treg cells in vivo. Overall, our results suggest that HpHSP60 could act on macrophages to trigger the expression of IL-10 and TGF-β, thereby leading to an increase in Treg cells and inhibition of T-cell proliferation.

Keywords: Helicobacter pylori-derived heat shock protein 60; Interlukin-10; Regulatory T-cells; Transforming growth factor β.

MeSH terms

Animals
CD3 Complex / immunology
Cell Death / drug effects
Cell Proliferation / drug effects
Chaperonin 60 / genetics
Chaperonin 60 / immunology
Chaperonin 60 / metabolism*
Chaperonin 60 / pharmacology*
Cyclin-Dependent Kinase 4 / metabolism
Cytokines / metabolism
Female
Gastric Mucosa / immunology
Gastric Mucosa / pathology
Gene Expression Regulation, Bacterial
Helicobacter Infections / immunology
Helicobacter pylori / genetics
Helicobacter pylori / metabolism*
Helicobacter pylori / pathogenicity
Humans
Immunosuppression Therapy
Inflammation
Interleukin-10 / metabolism
Interleukin-8 / metabolism
Leukocytes, Mononuclear / drug effects
Leukocytes, Mononuclear / immunology
Mice, Inbred BALB C
Monocytes / drug effects
Monocytes / metabolism
T-Lymphocytes, Regulatory / drug effects*
T-Lymphocytes, Regulatory / immunology
THP-1 Cells
Transforming Growth Factor beta / metabolism
Virulence Factors / immunology*
Virulence Factors / metabolism*

Substances

CD3 Complex
Chaperonin 60
Cytokines
IL10 protein, human
Interleukin-8
Transforming Growth Factor beta
Virulence Factors
Interleukin-10
Cyclin-Dependent Kinase 4