CPAF, HSP60 and MOMP antigens elicit pro-inflammatory cytokines production in the peripheral blood mononuclear cells from genital Chlamydia trachomatis-infected patients

Cheong, Heng Choon; Lee, Chalystha Yie Qin; Cheok, Yi Ying; Shankar, Esaki M.; Sabet, Negar Shafiei; Tan, Guan Huat; Movahed, Elaheh; Yeow, Tee Cian; Sulaiman, Sofiah; Wong, Won Fen; Looi, Chung Yeng; Gupta, Rishein; Hassan, Jamiyah; Arulanandam, Bernard P.; AbuBakar, Sazaly

doi:10.1016/j.imbio.2018.10.010

Cited by 15 publications

(11 citation statements)

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“…Perinatal exposure to C. trachomatis can result in conjunctivitis and lower respiratory tract infection in newborns [73,74]. The disease pathogenesis following C. trachomatis is attributable to the secretion of pathogen immunogenic molecules such as chlamydial protease-like activity factor (CPAF), which paralyzes the activity of neutrophils [111,112], virulence factors such as the 7.5-kb plasmid [113,114], and the ability of the pathogen to alter the proteome profile of the host cells [115,116].…”

Section: Introductionmentioning

confidence: 99%

Chlamydiaceae: Diseases in Primary Hosts and Zoonosis

et al. 2019

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Bacteria of the Chlamydiaceae family are a type of Gram-negative microorganism typified by their obligate intracellular lifestyle. The majority of the members in the Chlamydiaceae family are known pathogenic organisms that primarily infect the host mucosal surfaces in both humans and animals. For instance, Chlamydia trachomatis is a well-known etiological agent for ocular and genital sexually transmitted diseases, while C. pneumoniae has been implicated in community-acquired pneumonia in humans. Other chlamydial species such as C. abortus, C. caviae, C. felis, C. muridarum, C. pecorum, and C. psittaci are important pathogens that are associated with high morbidities in animals. Importantly, some of these animal pathogens have been recognized as zoonotic agents that pose a significant infectious threat to human health through cross-over transmission. The current review provides a succinct recapitulation of the characteristics as well as transmission for the previously established members of the Chlamydiaceae family and a number of other recently described chlamydial organisms.

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Section: Introductionmentioning

confidence: 99%

Chlamydiaceae: Diseases in Primary Hosts and Zoonosis

et al. 2019

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“…A study by Massari and colleagues delineated that MOMP proteosomes stimulated IL-6 and IL-8 secretions in endocervical epithelial cells [ 91 ]. Recently, Cheong et al reported that MOMP triggered the release of pro-inflammatory cytokines in peripheral blood mononuclear cells (PBMCs) from C. trachomatis -infected patients [ 92 ]. The complexity of chlamydial diseases demands further investigations into the mechanisms by which chlamydial antigens activate host cell inflammatory responses at the site of colonization and infection for the disease pathogenesis, which are essential for proper insights in developing improved therapeutic strategies.…”

Section: Discussionmentioning

confidence: 99%

Suppressors of Cytokine Signaling (SOCS)1 and SOCS3 Proteins Are Mediators of Interleukin-10 Modulation of Inflammatory Responses Induced byChlamydia muridarumand Its Major Outer Membrane Protein (MOMP) in Mouse J774 Macrophages

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Sahu

Dixit

et al. 2020

Mediators of Inflammation

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The immunopathology of chlamydial diseases is exacerbated by a broad-spectrum of inflammatory mediators, which we reported are inhibited by IL-10 in macrophages. However, the chlamydial protein moiety that induces the inflammatory mediators and the mechanisms by which IL-10 inhibits them are unknown. We hypothesized that Chlamydia major outer membrane protein (MOMP) mediates its disease pathogenesis, and the suppressor of cytokine signaling (SOCS)1 and SOCS3 proteins are mediators of the IL-10 inhibitory actions. Our hypothesis was tested by exposing mouse J774 macrophages to chlamydial stimulants (live Chlamydia muridarum and MOMP) with and without IL-10. MOMP significantly induced several inflammatory mediators (IL-6, IL-12p40, CCL5, CXCL10), which were dose-dependently inhibited by IL-10. Chlamydial stimulants induced the mRNA gene transcripts and protein expression of SOCS1 and SOCS3, with more SOCS3 expression. Notably, IL-10 reciprocally regulated their expression by reducing SOCS1 and increasing SOCS3. Specific inhibitions of MAPK pathways revealed that p38, JNK, and MEK1/2 are required for inducing inflammatory mediators as well as SOCS1 and SOCS3. Chlamydial stimulants triggered an M1 pro-inflammatory phenotype evidently by an enhanced nos2 (M1 marker) expression, which was skewed by IL-10 towards a more M2 anti-inflammatory phenotype by the increased expression of mrc1 and arg1 (M2 markers) and the reduced SOCS1/SOCS3 ratios. Neutralization of endogenously produced IL-10 augmented the secretion of inflammatory mediators, reduced SOCS3 expression, and skewed the chlamydial M1 to an M2 phenotype. Inhibition of proteasome degradation increased TNF but decreased IL-10, CCL5, and CXCL10 secretion by suppressing SOCS1 and SOCS3 expressions and dysregulating their STAT1 and STAT3 transcription factors. Our data show that SOCS1 and SOCS3 are regulators of IL-10 inhibitory actions, and underscore SOCS proteins as therapeutic targets for IL-10 control of inflammation for Chlamydia and other bacterial inflammatory diseases.

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“…Inflammation is considered one of the most common consequence of persistent chlamydial infections (Cheong et al, 2018; Hou et al, 2018; Jia et al, 2019). To investigate the potential roles of TC0668 in inducing inflammatory- and fibrosis-related pathogenesis, a PPI network analysis of differentially expressed proteins at 18 h p.i was performed.…”

Section: Discussionmentioning

confidence: 99%

iTRAQ-Based Quantitative Proteomics Analysis of HeLa Cells Infected With Chlamydia muridarum TC0668 Mutant and Wild-Type Strains

et al. 2019

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Chlamydia muridarum, an obligate intracellular pathogen, was used to establish a murine model of female upper genital tract infection by Chlamydia trachomatis. TC0668 in C. muridarum is a hypothetical chromosomal virulence protein that is involved in upper genital tract pathogenesis. The infection of mice with the C. muridarum TC0668-mutant (G216*) strain results in less pathological damage in the upper genital tract. In this study, an isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics analysis was performed to identify differentially expressed proteins between TC0668 wild-type (TC0668wt) and TC0668 mutant (TC0668mut) strains at 6, 12, 18, and 24 h post-infection (p.i.). Of the 550 proteins differentially expressed at 18 h p.i., 222 and 328 were up-regulated and down-regulated, respectively, inTC0668mut-infected cells. The expression of seven up-regulated proteins (encoded by SRPRB, JAK1, PMM1, HLA-DQB1, THBS1, ITPR1, and BCAP31) and three down-regulated proteins (encoded by MAPKAPK2, TRAFD1, and IFI16) from the iTRAQ analysis were validated using quantitative real-time (qRT)-PCR. The qRT-PCR results were consistent with those of iTRAQ. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that the differentially expressed proteins primarily participated in inflammatory responses, fibrosis, metabolic processes, and complement coagulation cascades, and were mainly enriched in the phosphatidylinositol 3′-kinase (PI3K)/Akt, nuclear factor kappa-B (NF-κB), and other signaling pathways. Using western-blotting and immunofluorescence detection, significant differences in activation of the PI3K/Akt and NF-κB signaling pathways were observed between the TC0668wt- and TC0668mut-infected cells. Differentially expressed proteins linked with inflammation and fibrosis were used in a protein-protein interaction network analysis. The results suggest that TC0668 may play a pivotal role in C. muridarum-induced genital pathology by inducing inflammatory responses and fibrosis, which may involve the activation of the PI3K/Akt and NF-κB signaling pathways.

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CPAF, HSP60 and MOMP antigens elicit pro-inflammatory cytokines production in the peripheral blood mononuclear cells from genital Chlamydia trachomatis-infected patients

Cited by 15 publications

References 43 publications

Chlamydiaceae: Diseases in Primary Hosts and Zoonosis

Chlamydiaceae: Diseases in Primary Hosts and Zoonosis

Suppressors of Cytokine Signaling (SOCS)1 and SOCS3 Proteins Are Mediators of Interleukin-10 Modulation of Inflammatory Responses Induced byChlamydia muridarumand Its Major Outer Membrane Protein (MOMP) in Mouse J774 Macrophages

iTRAQ-Based Quantitative Proteomics Analysis of HeLa Cells Infected With Chlamydia muridarum TC0668 Mutant and Wild-Type Strains

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