ORIGINAL RESEARCH article
Front. Immunol.
Sec. Microbial Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1645250
The N-terminal domain of Chlamydia psittaci Pmp19G modulates macrophage autophagy by targeting the NOD1 receptor and the ATG16L1–RAB7 signaling pathway
Provisionally accepted
- China Agricultural University, Beijing, China
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Introduction: Chlamydia psittaci (C. psittaci), a zoonotic intracellular Gram-negative bacterium, is responsible for human infections presenting as flu-like fever and community-acquired pneumonia. Previous studies have implicated polymorphic membrane (Pmp) G in tissue tropism and induction of immune responses. However, the mechanisms by which Pmp19G promotes C. psittaci infection and immune evasion—especially via macrophage subversion remain poorly understood. Methods and Results: This study demonstrates that both C. psittaci and recombinant C. psittaci-specific Pmp19G protein activated autophagy in macrophages. This activation was characterized by increased autophagosome formation, conversion of LC3-I to LC3-II, and accumulation of p62/SQSTM1, while lysosomal associated membrane protein 1 (LAMP1), a late autophagy biomarker, remained unaffected. Utilizing pull-down assays coupled with co-immunoprecipitation, we identified the NOD1 receptor as an interactor with the N-terminal domain of Pmp19G. Subsequent analysis confirmed activation of the NOD1-ATG16L1 signaling pathway. NOD1 knockout or knockdown significantly impaired Pmp19G-mediated autophagic flux. Furthermore, treatment with Pmp19G enhanced the recruitment of RAB7 during the late stages of autophagy. Discussion: Our findings indicate that Pmp19G regulates macrophage autophagy through distinct mechanisms in early and late phases: activation of the NOD1-ATG16L1 signaling pathway initiates early autophagy, while enhanced RAB7 recruitment inhibits autophagosome-lysosome fusion during late autophagy. Collectively, Pmp19G-involved manipulation of the autophagic process represents a critical strategy employed by C. psittaci to evade host immune defenses, leading bacterial survival and spread.
Keywords: Chlamydia psittaci, Pmp19G, NOD1, Macrophages, Autophagy, immuneevasion
Received: 11 Jun 2025; Accepted: 21 Aug 2025.
Copyright: © 2025 Li, Wang, Cui, Huang, Zhang, He and He. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Cheng He, China Agricultural University, Beijing, China
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