GSDMD-mediated pyroptosis restrains intracellular Chlamydia trachomatis growth in macrophages

Ping Jiang; Hongzhi Chen; Xiaojing Feng; Huiqi Xie; Mengjie Jiang; Danning Xu; Haoneng Tang; Ningjie Zhang; Jianlin Chen; Lei Zhang; Lingli Tang

doi:10.3389/fcimb.2023.1116335

GSDMD-mediated pyroptosis restrains intracellular Chlamydia trachomatis growth in macrophages

Front Cell Infect Microbiol. 2023 Mar 16:13:1116335. doi: 10.3389/fcimb.2023.1116335. eCollection 2023.

Authors

Affiliations

¹ Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
² National Clinical Research Center for Metabolic Disease, Key Laboratory of Diabetes Immunology, Ministry of Education, Metabolic Syndrome Research Center, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
³ Department of Blood Transfusion, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁴ Reproductive Medicine Center, Department of Obstetrics and Gynecology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁵ Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Abstract

Pyroptosis, a type of programmed necrosis associated with inflammatory, is a host defense mechanism against microbial infections. Although Chlamydia has been shown to induce pyroptosis, whether pyroptosis directly impacts the growth of Chlamydia has not been demonstrated. In this study, we found that C. trachomatis L2 infection of the mouse macrophage RAW 264.7 cells induced pyroptosis by monitoring the ultrastructural changes under transmission electron microscopy and the release of LDH and IL-1β. More importantly, this C. trachomatis-triggered pyroptosis with activation of caspase-1 and caspase-11 was also accompanied by gasdermin D (GSDMD) activation. Suppression of these two inflammatory caspases inhibited GSDMD activation. Interestingly, the C. trachomatis-triggered pyroptosis significantly inhibited the intracellular growth of C. trachomatis since inactivation of either GSDMD or caspase-1/11 significantly rescued infectious C. trachomatis yields, which suggests pyroptosis response can be utilized as an intrinsic mechanism to restrict C. trachomatis intracellular infection in addition to the well- documented extrinsic mechanisms by recruiting and enhancing inflammatory responses. This study may reveal novel targets for attenuating C. trachomatis infectivity and/or pathogenicity.

Keywords: Chlamydia trachomatis; GSDMD; caspase-1; caspase-11; macrophage; pyroptosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Caspase 1
Caspases
Chlamydia trachomatis
Intracellular Signaling Peptides and Proteins*
Macrophages
Mice
Pyroptosis*

Substances

Intracellular Signaling Peptides and Proteins
Caspases
Caspase 1

Grants and funding

This study was supported by Natural Science Foundation of Changsha City (grant number kq2202415) and Natural Science Foundation of Hunan Province (grant number 2018JJ2559).