Less inhibition of interferon-gamma to organism growth in host cells may contribute to the high susceptibility of C3H mice to Chlamydia trachomatis lung infection

ABSTRACT Chlamydia trachomatis is an obligate intracellular gram-negative bacterium responsible for a wide spectrum of diseases in humans. Both genital and ocular C. trachomatis infections are associated with tissue inflammation and pathology. Dendritic cells (DC) play an important role in both innate and adaptive immune responses to microbial pathogens and are a source of inflammatory cytokines. To determine the potential contribution of DC to the inflammatory process, human DC were infected with C. trachomatis serovar E or L2. Both C. trachomatis serovars were found to infect and replicate in DC. Upon infection, DC up-regulated the expression of costimulatory (B7-1) and cell adhesion (ICAM-1) molecules. Furthermore, chlamydial infection induced the secretion of interleukin-1β (IL-1β), IL-6, IL-8, IL-12p70, IL-18, and tumor necrosis factor alpha (TNF-α). The mechanisms involved in Chlamydia-induced IL-1β and IL-18 secretion differed from those of the other cytokines. Chlamydia-induced IL-1β and IL-18 secretion required infection with viable bacteria and was associated with the Chlamydia-induced activation of caspase-1 in infected host cells. In contrast, TNF-α and IL-6 secretion did not require that the Chlamydia be viable, suggesting that there are at least two mechanisms involved in the Chlamydia-induced cytokine secretion in DC. Interestingly, an antibody to Toll-like receptor 4 inhibited Chlamydia-induced IL-1β, IL-6, and TNF-α secretion. The data herein demonstrate that DC can be infected by human C. trachomatis serovars and that chlamydial components regulate the secretion of various cytokines in DC. Collectively, these data suggest that DC play a role in the inflammatory processes caused by chlamydial infections.

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Identification of differentially expressed circular RNAs in HeLa cells infected with Chlamydia trachomatis

Pathogens and Disease ◽

10.1093/femspd/ftz062 ◽

2019 ◽

Vol 77 (7) ◽

Author(s):

Yuanjun Liu ◽

Chunmin Hu ◽

Yina Sun ◽

Haoqing Wu ◽

Xiaojun Chen ◽

...

Keyword(s):

Chlamydia Trachomatis ◽

Signaling Pathways ◽

Hela Cells ◽

Expression Profiles ◽

Quantitative Polymerase Chain Reaction ◽

Host Cells ◽

Differentially Expressed ◽

Chlamydia Infection ◽

Circular Rnas ◽

Mrna Microarray

ABSTRACT Non-coding circular RNAs (circRNAs) have been shown to have important roles in many diseases; however, no study has indicated circRNAs are involved in Chlamydia trachomatis infection. In this study, we used circRNA microarray to measure the global circRNA expression profiles in HeLa cells with or without C. trachomatis serovar E (Ct.E) infection. CircRNA/miRNA/mRNA interactions were predicted and bioinformatics analyses were performed. The differentially expressed circRNAs were selected according to our criterion for validation by reverse-transcription and quantitative polymerase chain reaction (RT-qPCR). The mRNA microarray was used to detect the mRNA expression profiles after Ct.E infection. Among 853 differentially expressed circRNAs, 453 were upregulated and 400 were downregulated after Ct.E infection. Target miRNAs and miRNA-targeted mRNAs of these circRNAs were predicted. RT-qPCR analysis indicated hsa_circRNA_001226, hsa_circRNA_007046 and hsa_circRNA_400027 were elevated similar to those determined in the circRNA microarray analysis. The mRNA microarray results showed 915 genes were upregulated and 619 genes were downregulated after Ct.E infection. Thirty-four differentially expressed genes overlapped in the bioinformatics and mRNA microarray results. KEGG pathway analysis revealed several signaling pathways, including endocytosis, MAPK and PI3P-Akt signaling pathways, that were targeted by circRNAs may play important roles in Chlamydia infection. This study provides evidence that circRNAs in host cells are involved in the process of Chlamydia infection.

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Fluorescence-Reported Allelic Exchange Mutagenesis-Mediated Gene Deletion Indicates a Requirement for Chlamydia trachomatis Tarp during In Vivo Infectivity and Reveals a Specific Role for the C Terminus during Cellular Invasion

Infection and Immunity ◽

10.1128/iai.00841-19 ◽

2020 ◽

Vol 88 (5) ◽

Author(s):

Susmita Ghosh ◽

Elizabeth A. Ruelke ◽

Joshua C. Ferrell ◽

Maria D. Bodero ◽

Kenneth A. Fields ◽

...

Keyword(s):

Chlamydia Trachomatis ◽

Host Cell ◽

Host Cells ◽

Actin Binding ◽

Wild Type ◽

Content Type ◽

Allelic Exchange ◽

Binding Domains

ABSTRACT The translocated actin recruiting phosphoprotein (Tarp) is a multidomain type III secreted effector used by Chlamydia trachomatis. In aggregate, existing data suggest a role of this effector in initiating new infections. As new genetic tools began to emerge to study chlamydial genes in vivo, we speculated as to what degree Tarp function contributes to Chlamydia’s ability to parasitize mammalian host cells. To address this question, we generated a complete tarP deletion mutant using the fluorescence-reported allelic exchange mutagenesis (FRAEM) technique and complemented the mutant in trans with wild-type tarP or mutant tarP alleles engineered to harbor in-frame domain deletions. We provide evidence for the significant role of Tarp in C. trachomatis invasion of host cells. Complementation studies indicate that the C-terminal filamentous actin (F-actin)-binding domains are responsible for Tarp-mediated invasion efficiency. Wild-type C. trachomatis entry into HeLa cells resulted in host cell shape changes, whereas the tarP mutant did not. Finally, using a novel cis complementation approach, C. trachomatis lacking tarP demonstrated significant attenuation in a murine genital tract infection model. Together, these data provide definitive genetic evidence for the critical role of the Tarp F-actin-binding domains in host cell invasion and for the Tarp effector as a bona fide C. trachomatis virulence factor.

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Chlamydia trachomatis Cellular Exit Alters Interactions with Host Dendritic Cells

Infection and Immunity ◽

10.1128/iai.00046-17 ◽

2017 ◽

Vol 85 (5) ◽

Cited By ~ 1

Author(s):

Ashley M. Sherrid ◽

Kevin Hybiske

Keyword(s):

Dendritic Cells ◽

Dendritic Cell ◽

Chlamydia Trachomatis ◽

Innate Immune ◽

Host Cells ◽

Bacterial Survival ◽

Content Type ◽

Innate Immune Signaling ◽

Host Membrane ◽

Membrane Bound

ABSTRACT The strategies utilized by pathogens to exit host cells are an area of pathogenesis which has received surprisingly little attention, considering the necessity of this step for infections to propagate. Even less is known about how exit through these pathways affects downstream host-pathogen interactions and the generation of an immune response. Chlamydia trachomatis exits host epithelial cells through two equally active mechanisms: lysis and extrusion. Studies have characterized the outcome of interactions between host innate immune cells, such as dendritic cells and macrophages, and free, extracellular Chlamydia bacteria, such as those resulting from lysis. Exit via extrusion generates a distinct, host-membrane-bound compartment of Chlamydia separate from the original infected cell. In this study, we assessed the effect of containment within extrusions upon the interaction between Chlamydia and host dendritic cells. Extrusion dramatically affected the outcome of Chlamydia-dendritic cell interactions for both the bacterium and the host cell. Dendritic cells rapidly underwent apoptosis in response to engulfment of an extrusion, while uptake of an equivalent dose of free Chlamydia had no such effect. Containment within an extrusion also prolonged bacterial survival within dendritic cells and altered the initial innate immune signaling by the dendritic cell.

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Chlamydia trachomatis-infected cells and uninfected-bystander cells exhibit diametrically opposed responses to interferon gamma

Scientific Reports ◽

10.1038/s41598-018-26765-y ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 6

Author(s):

Joyce A. Ibana ◽

Shardulendra P. Sherchand ◽

Francis L. Fontanilla ◽

Takeshi Nagamatsu ◽

Danny J. Schust ◽

...

Keyword(s):

Chlamydia Trachomatis ◽

Interferon Gamma ◽

Infected Cells ◽

Bystander Cells

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Structure and Metal Binding Properties of Chlamydia trachomatis YtgA

Journal of Bacteriology ◽

10.1128/jb.00580-19 ◽

2019 ◽

Vol 202 (1) ◽

Cited By ~ 2

Author(s):

Zhenyao Luo ◽

Stephanie L. Neville ◽

Rebecca Campbell ◽

Jacqueline R. Morey ◽

Shruti Menon ◽

...

Keyword(s):

Chlamydia Trachomatis ◽

Transition Metal ◽

Metal Binding ◽

Developed Countries ◽

Biochemical Properties ◽

Host Cells ◽

Transmitted Infection ◽

Content Type ◽

Sexually Transmitted ◽

Serious Disease

Chlamydia trachomatis is the most common bacterial sexually transmitted infection in developed countries, with an estimated global prevalence of 4.2% in the 15- to 49-year age group. Although infection is asymptomatic in more than 80% of infected women, about 10% of cases result in serious disease. Infection by C. trachomatis is dependent on the ability to acquire essential nutrients, such as the transition metal iron, from host cells. In this study, we show that iron is the most abundant transition metal in C. trachomatis and report the structural and biochemical properties of the iron-recruiting protein YtgA. Knowledge of the high-resolution structure of YtgA will provide a platform for future structure-based antimicrobial design approaches.

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