Chlamydia trachomatis plasmid-encoding Pgp3 protein induces secretion of distinct inflammatory signatures from HeLa cervical epithelial cells

Cheong, Heng Choon; Cheok, Yi Ying; Chan, Yee Teng; Tang, Ting; Sulaiman, Sofiah; Looi, Chung Yeng; Gupta, Rishein; Arulanandam, Bernard P.; Chang, Li-Yen; Wong, Won Fen

doi:10.1186/s12866-023-02802-3

Cited by 5 publications

(4 citation statements)

References 66 publications

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“…Chemokines belonging to the C-X-C family are known to play a role in leukocyte recruitment and regulate the tumor microenvironment by controlling tumor cell proliferation, metastasis, invasion, angiogenesis, and therapeutic resistance [ 23 ]. Numerous studies on Chlamydia trachomatis have demonstrated its capacity to upregulate C-X-C chemokine levels at the site of infection, thereby inducing an intense inflammatory response [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Evidence for the presence of Borrelia burgdorferi in invasive breast cancer tissues

Patel,

Thippani,

Jathan

et al. 2024

EuJMI

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Borrelia burgdorferi, the causative agent of Lyme disease, has recently been demonstrated to infect and enhance the invasive properties of breast cancer cells, while also influencing the expression of inflammatory chemokines (CXCL8 and CXCL10). This study investigates the presence of B. burgdorferi in invasive breast cancer tissues using commercially available, FDA-approved breast cancer tissue microarrays consisting of 350 ductal, 32 lobular, and 22 intraductal invasive breast carcinomas, alongside 29 normal breast tissues. Employing fluorescent immunohistochemical staining and high-resolution imaging, the findings revealed that approximately 20% of invasive lobular and ductal carcinomas, followed by 14% of intraductal carcinomas, tested positive for B. burgdorferi, while all normal breast tissues tested negative. PCR analysis further confirmed the presence of B. burgdorferi DNA in breast cancer tissues. Moreover, 25% of B. burgdorferi-positive tissues exhibited expression of both chemokines, CXCL8 and CXCL10, which was not observed in B. burgdorferi-negative tissues. Analysis of available patient data, including age, indicated a correlation between older patients and B. burgdorferi-positive tissues. This study validates the presence of B. burgdorferi in invasive breast cancer tissues and highlights the involvement of key CXCL family members associated with inflammatory processes.

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Section: Discussionmentioning

confidence: 99%

Evidence for the presence of Borrelia burgdorferi in invasive breast cancer tissues

Patel,

Thippani,

Jathan

et al. 2024

EuJMI

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“…Purified Pgp3 protein stimulates macrophages to release inflammatory cytokines (Li et al, 2008 ). It induces the expression of a series of host inflammatory cytokine genes, including interleukin-6 (IL-6), IL-8, tumor necrosis factor alpha-induced protein 3 (TNFAIP3), and chemokine C-X-C motif ligand 1 (CXCL1), after stimulating HeLa cells (Cheong et al, 2023 ). The involvement of tumor necrosis factor receptor 1 (TNFR1) in Chlamydia pathogenesis is supported by crystal analyses that have shown that the Pgp3 C-terminal trimerization domain resembles the TNF-like domain (Galaleldeen et al, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

Tryptophan residue of plasmid-encoded Pgp3 is important for Chlamydia muridarum to induce hydrosalpinx in mice

Huang

Sun

et al. 2023

Front. Microbiol.

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The crucial role of plasmid-encoded protein Pgp3 in Chlamydia pathogenesis has been demonstrated in various animal models. Previous studies have revealed that the Pgp3-deficient C. muridarum mutant fails to induce hydrosalpinx after vaginal inoculation in mice. Structural analysis of C. trachomatis Pgp3 trimer has indicated that Trp234 may play a critical role in trimeric crystal packing interactions and that Tyr197 is involved at predominant cation-binding sites. In this study, we constructed C. muridarum transformants harboring Pgp3, Trp234, or Tyr197 point mutations (Pgp3W234A and Pgp3Y197A). C3H/HeJ mice infected with Pgp3W234A mutant failed to induce severe hydrosalpinx in the oviduct tissue, which largely phenocopied the full-length Pgp3-deficient C. muridarum. The Pgp3Y197A variant induced an intermediate severity of pathology. The attenuated pathogenicity caused by the Pgp3W234A mutant may be due to its decreased survival in the lower genital tracts of mice, reduced ascension to the oviduct, and milder induction of inflammatory cell infiltration in the oviduct tissue. Thus, our results point to an important amino acid residue involved in Pgp3 virulence, providing a potential therapeutic target for chlamydial infection.

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“…The interaction of C. trachomatis proteins with host proteins involves altering vesicular transport in extracellular vesicles, regulating cell survival pathways, and suppressing the innate host immune response. The Chlamydial effector proteins interfere with the host’s innate immune response, such as INCs, TepP ( 35 ), CPAF, Pgp3 ( 36 ), Pgp4 ( 37 ) and 60 other proteins ( 38 ), which promote intracellular survival of Chlamydia and limit the host response to infection. RBs continue to differentiate in inclusions and, at later stages, asynchronously undergo secondary differentiation to create new EBs.…”

Section: Pathogenesis and Immunitymentioning

confidence: 99%

Insights into innate immune cell evasion by Chlamydia trachomatis

Wang,

Wu,

Fang

et al. 2024

Front. Immunol.

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Chlamydia trachomatis, is a kind of obligate intracellular pathogen. The removal of C. trachomatis relies primarily on specific cellular immunity. It is currently considered that CD4+ Th1 cytokine responses are the major protective immunity against C. trachomatis infection and reinfection rather than CD8+ T cells. The non-specific immunity (innate immunity) also plays an important role in the infection process. To survive inside the cells, the first process that C. trachomatis faces is the innate immune response. As the “sentry” of the body, mast cells attempt to engulf and remove C. trachomatis. Dendritic cells present antigen of C. trachomatis to the “commanders” (T cells) through MHC-I and MHC-II. IFN-γ produced by activated T cells and natural killer cells (NK) further activates macrophages. They form the body’s “combat troops” and produce immunity against C. trachomatis in the tissues and blood. In addition, the role of eosinophils, basophils, innate lymphoid cells (ILCs), natural killer T (NKT) cells, γδT cells and B-1 cells should not be underestimated in the infection of C. trachomatis. The protective role of innate immunity is insufficient, and sexually transmitted diseases (STDs) caused by C. trachomatis infections tend to be insidious and recalcitrant. As a consequence, C. trachomatis has developed a unique evasion mechanism that triggers inflammatory immunopathology and acts as a bridge to protective to pathological adaptive immunity. This review focuses on the recent advances in how C. trachomatis evades various innate immune cells, which contributes to vaccine development and our understanding of the pathophysiologic consequences of C. trachomatis infection.

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Chlamydia trachomatis plasmid-encoding Pgp3 protein induces secretion of distinct inflammatory signatures from HeLa cervical epithelial cells

Cited by 5 publications

References 66 publications

Evidence for the presence of Borrelia burgdorferi in invasive breast cancer tissues

Evidence for the presence of Borrelia burgdorferi in invasive breast cancer tissues

Tryptophan residue of plasmid-encoded Pgp3 is important for Chlamydia muridarum to induce hydrosalpinx in mice

Insights into innate immune cell evasion by Chlamydia trachomatis

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