Chlamydia psittaci Plasmid-Encoded CPSIT_P7 Elicits Inflammatory Response in Human Monocytes via TLR4/Mal/MyD88/NF-κB Signaling Pathway

Abstract

The chlamydial plasmid, an essential virulence factor, encodes plasmid proteins that play important roles in chlamydial infection and the corresponding immune response. However, the virulence factors and the molecular mechanisms of Chlamydia psittaci are not well understood. In the present study, we investigated the roles and mechanisms of the plasmid-encoded protein CPSIT_P7 of C. psittaci in regulating the inflammatory response in THP-1 cells (human monocytic leukemia cell line). Based on cytokine arrays, CPSIT_P7 induces the expression of interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1) in THP-1 cells. Moreover, the expression levels of IL-6, IL-8, and MCP-1 stimulated by CPSIT_P7 declined after silencing of the Toll-like receptor 4 (TLR4) gene using small interfering RNA and transfection of a dominant negative plasmid encoding TLR4 (pZERO-hTLR4). We further demonstrated that transfection with the dominant negative plasmid encoding MyD88 (pDeNy-hMyD88) and the dominant negative plasmid encoding Mal (pDeNy-hMal) could also abrogate the expression of the corresponding proteins. Western blot and immunofluorescence assay results showed that CPSIT_P7 could activate nuclear factor κB (NF-κB) signaling pathways in THP-1 cells. Altogether, our results indicate that the CPSIT_P7 induces the TLR4/Mal/MyD88/NF-κB signaling axis and therefore contributes to the inflammatory cytokine response.

Host inflammatory response is the major factor in the progression of Chlamydia psittaci pneumonia

“…immune response against C. psittaci infection, providing an invaluable opportunity to understand psittacosis pathogenesis. When C. psittaci invades human or animal cells or tissues, a variety of inflammatory cytokines are upregulated, particularly IL-6, IL-8, MCP-1, GM-CSF, TNF-a, and anti-inflammatory factor IL-10 (20-22), and the TLR4/Mal/MyD88/NF-kB signaling axis is activated, which contributes to the innate immune responses (23), which may play different pathogenic roles in the process of C. psittaci infection. Consistent with the previous findings, we found that levels of a variety of cytokines, such as IL-6, IL-1RN, and TNF-a, increased rapidly in the pneumonia cases, thereby accelerating the inflammatory response (24).…”

Redox Homeostasis in Poultry: Regulatory Roles of NF-κB

“…In great contrast, inhibition of TLR2, MyD88, and NF-κB in HD11 cells was reported to significantly decrease IL-6 and IL-10 cytokine levels associated with significantly enhanced NO production and phagocytosis [ 307 ]. The plasmid-encoded protein CPSIT_P7 of Chlamydia psittaci was shown to induce the TLR4/Mal/MyD88/NF-κB signaling axis and orchestrate the inflammatory cytokine response [ 308 ].…”

Clinical identification and microbiota analysis of Chlamydia psittaci- and Chlamydia abortus- pneumonia by metagenomic next-generation sequencing

“…Meanwhile, microorganisms such as Bacillus spp., Actinomyces spp. and even Chlamydia psittaci or Chlamydia abortus can directly or indirectly regulate the expression of host pro-inflammatory factors or important disease-related genes such as METTLE3, thus affecting the physiological and pathological processes of the host ( Pan et al., 2017 ; Chen et al., 2020a ; Gómez-García et al., 2022 ; Wang et al., 2022 ; Xu et al., 2022 ; Zhang et al., 2022b ). These previous studies will help us to conduct future research on the direction of microbial-host immune interactions in terms of how microbes and their metabolites regulate pro-inflammatory signaling pathways, and how microbes and their metabolites are involved in the regulation of signaling pathways and expression of key targets related to important diseases such as inflammation or tumours.…”