Mycoplasma genitalium Protein of Adhesion Suppresses T Cell Activation via CypA-CaN-NFAT Pathway

Dan Luo; Haodang Luo; Xiaoliang Yan; Aihua Lei; Jun He; Yating Liao; Kailan Peng; Xia Li; Youyuan Ye; Li Chen; Zhuo Zeng; Hua Xiao; Yanhua Zeng

doi:10.1128/spectrum.04503-22

Microbiology Spectrum (Jun 2023)

Mycoplasma genitalium Protein of Adhesion Suppresses T Cell Activation via CypA-CaN-NFAT Pathway

Dan Luo,
Haodang Luo,
Xiaoliang Yan,
Aihua Lei,
Jun He,
Yating Liao,
Kailan Peng,
Xia Li,
Youyuan Ye,
Li Chen,
Zhuo Zeng,
Hua Xiao,
Yanhua Zeng

Affiliations

Dan Luo: Institute of Pathogenic Biology, Basic Medical School, Hengyang Medical School, University of South China, Hengyang, Hunan, China
Haodang Luo: Institute of Pathogenic Biology, Basic Medical School, Hengyang Medical School, University of South China, Hengyang, Hunan, China
Xiaoliang Yan: Institute of Pathogenic Biology, Basic Medical School, Hengyang Medical School, University of South China, Hengyang, Hunan, China
Aihua Lei: Institute of Pathogenic Biology, Basic Medical School, Hengyang Medical School, University of South China, Hengyang, Hunan, China
Jun He: Department of Clinical Laboratory, the Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
Yating Liao: Institute of Pathogenic Biology, Basic Medical School, Hengyang Medical School, University of South China, Hengyang, Hunan, China
Kailan Peng: Institute of Pathogenic Biology, Basic Medical School, Hengyang Medical School, University of South China, Hengyang, Hunan, China
Xia Li: Institute of Pathogenic Biology, Basic Medical School, Hengyang Medical School, University of South China, Hengyang, Hunan, China
Youyuan Ye: Institute of Pathogenic Biology, Basic Medical School, Hengyang Medical School, University of South China, Hengyang, Hunan, China
Li Chen: Institute of Pathogenic Biology, Basic Medical School, Hengyang Medical School, University of South China, Hengyang, Hunan, China
Zhuo Zeng: Institute of Pathogenic Biology, Basic Medical School, Hengyang Medical School, University of South China, Hengyang, Hunan, China
Hua Xiao: Institute of Pathogenic Biology, Basic Medical School, Hengyang Medical School, University of South China, Hengyang, Hunan, China
Yanhua Zeng: Institute of Pathogenic Biology, Basic Medical School, Hengyang Medical School, University of South China, Hengyang, Hunan, China

DOI: https://doi.org/10.1128/spectrum.04503-22
Journal volume & issue: Vol. 11, no. 3

Abstract

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ABSTRACT Mycoplasma genitalium is a prokaryotic microorganism that causes urogenital tract infections. M. genitalium protein of adhesion (MgPa) was essential for M. genitalium attachment and subsequent invasion into host cells. Our prior research confirmed that Cyclophilin A (CypA) was the binding receptor for MgPa and MgPa-CypA interaction can lead to the production of inflammatory cytokines. In this study, we revealed that the recombinant MgPa (rMgPa) could inhibit the CaN-NFAT signaling pathway to reduce the level of IFN-γ, IL-2, CD25, and CD69 in Jurkat cells by binding to the CypA receptor. Moreover, rMgPa inhibited the expressions of IFN-γ, IL-2, CD25, and CD69 in primary mouse T cells. Likewise, the expressions of these T cells activation-related molecules in CypA-siRNA-transfected cells and CypA−/− mouse primary T cell was strengthened by rMgPa. These findings showed that rMgPa suppressed T cell activation by downregulating the CypA-CaN-NFAT pathway, and as a result, acted as an immunosuppressive agent. IMPORTANCE Mycoplasma genitalium is a sexually transmitted bacterium that can co-infect with other infections and causes nongonococcal urethritis in males, cervicitis, pelvic inflammatory disease, premature birth, and ectopic pregnancy in women. The adhesion protein of M. genitalium (MgPa) is the primary virulence factor in the complicated pathogenicity of M. genitalium. This research proved that MgPa could interact with host cell Cyclophilin A (CypA) and prevent T cell activation by inhibiting Calcineurin (CaN) phosphorylation and NFAT nuclear translocation, which clarified the immunosuppression mechanism of M. genitalium to host T cells. Therefore, this study can provide a new idea that CypA can be used for a therapeutic or prophylactic target for M. genitalium infection.

Published in Microbiology Spectrum

ISSN: 2165-0497 (Online)
Publisher: American Society for Microbiology
Country of publisher: United States
LCC subjects: Science: Microbiology
Website: https://journals.asm.org/journal/spectrum

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