Chlamydia psittaci plasmid-encoded CPSIT_P7 induces macrophage polarization to enhance the antibacterial response through TLR4-mediated MAPK and NF-κB pathways

Siqin He; Chuan Wang; Yanru Huang; Simin Lu; Weiwei Li; Nan Ding; Chaoqun Chen; Yimou Wu

doi:10.1016/j.bbamcr.2022.119324

Chlamydia psittaci plasmid-encoded CPSIT_P7 induces macrophage polarization to enhance the antibacterial response through TLR4-mediated MAPK and NF-κB pathways

Biochim Biophys Acta Mol Cell Res. 2022 Oct;1869(10):119324. doi: 10.1016/j.bbamcr.2022.119324. Epub 2022 Jul 6.

Authors

Siqin He¹, Chuan Wang¹, Yanru Huang¹, Simin Lu¹, Weiwei Li¹, Nan Ding¹, Chaoqun Chen², Yimou Wu³

Affiliations

¹ Institute of Pathogenic Biology, Hengyang Medical College, University of South China, China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China; Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang, Hunan 421001, China.
² Institute of Pathogenic Biology, Hengyang Medical College, University of South China, China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China; Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang, Hunan 421001, China. Electronic address: [email protected].
³ Institute of Pathogenic Biology, Hengyang Medical College, University of South China, China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China; Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang, Hunan 421001, China. Electronic address: [email protected].

PMID: 35809864
DOI: 10.1016/j.bbamcr.2022.119324

Abstract

Although the protective effects of Chlamydia psittaci plasmid-encoded protein CPSIT_P7 as vaccine antigens to against chlamydial infection have been confirmed in our previous study, the function and mechanism of CPSIT_P7 inducing innate immunity in the antibacterial response remain unknown. Here, we found that plasmid protein CPSIT_P7 could induce M1 macrophage polarization upregulating the genes of the surface molecule CD86, proinflammatory cytokines (TNF-α, IL-6, and IL-1β), and antibacterial effector NO synthase 2 (iNOS). During M1 macrophage polarization, macrophages acquire phagocytic and microbicidal competence, which promotes the host antibacterial response. As we observed that CPSIT_P7-induced M1 macrophages could partially reduce the infected mice pulmonary Chlamydia psittaci load. Furthermore, CPSIT_P7 induced M1 macrophage polarization through the TLR4-mediated MAPK and NF-κB pathways. Collectively, our results highlight the effect of CPSIT_P7 on macrophage polarization and provide new insights into new prevention and treatment strategies for chlamydial infection.

Keywords: Antibacterial response; Chlamydia psittaci; Innate immune; MAPK; Macrophage polarization; NF-κB.

MeSH terms

Animals
Anti-Bacterial Agents / metabolism
Chlamydophila psittaci* / genetics
Chlamydophila psittaci* / metabolism
Macrophages / metabolism
Mice
Mitogen-Activated Protein Kinases / metabolism
NF-kappa B / genetics
NF-kappa B / metabolism
Plasmids / genetics
Psittacosis* / microbiology
Psittacosis* / prevention & control
Toll-Like Receptor 4 / genetics
Toll-Like Receptor 4 / metabolism

Substances

Anti-Bacterial Agents
NF-kappa B
Tlr4 protein, mouse
Toll-Like Receptor 4
Mitogen-Activated Protein Kinases