Host immune responses after hypoxic reactivation of IFN-Î³ induced persistent Chlamydia trachomatis infection

Jerchel, Stefan; Kaufhold, Inga; Schuchardt, Larissa; Shima, Kensuke; Rupp, Jan

doi:10.3389/fcimb.2014.00043

Cited by 17 publications

(11 citation statements)

References 44 publications

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“…Since C. trachomatis is known to affect cytokine gene expression in host cells during the postinfection period [17], we decided to investigate next the mRNA levels of IL-6 and FGF-2, two crucial proinflammatory cytokines, following exposure of McCoy and CWR-R1 cells to the pathogen.…”

Section: Resultsmentioning

confidence: 99%

Chlamydia trachomatis Growth and Cytokine mRNA Response in a Prostate Cancer Cell Line

Petyaev

Zigangirova

Morgunova

et al. 2019

Advances in Urology

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In the present paper, we report that C. trachomatis can be efficiently propagated and affect mRNA expression for two major cytokines, relevant to tumor progression, in CWR-R1 cells, a malignant prostate cell line. CWR-R1 and McCoy cells, a classic cell line for chlamydial research, were grown and infected with C. trachomatis under similar conditions. Cell monolayers were harvested for RNA analysis and immunostaining with major outer membrane protein (MOMP) antibody at 24, 48, and 72 hours of the postinfection (hpi) period. It was shown that the infectious cycle of chlamydial pathogen in CWR-R1 cells resembles the progression of C. trachomatis infection in McCoy cells but with a few important differences. First of all, the initial stage of C. trachomatis propagation in CWR-R1 cells (24 hpi) was characterized by larger inclusion bodies and more intense, specific immunofluorescent staining of infected cells as compared with McCoy cells. Moreover, there was a corresponding increase in infective progeny formation in CWR-R1 cells along with mRNA for EUO, a crucial gene controlling the early phase of the chlamydial development cycle (24 hpi). These changes were more minimal and became statistically insignificant at a later time point in the infectious cycle (48 hpi). Altogether, these data suggest that the early phase of C. trachomatis infection in CWR-R1 cells is accompanied by more efficient propagation of the pathogen as compared with the growth of C. trachomatis in McCoy cells. Furthermore, propagation of C. trachomatis in CWR-R1 cells leads to enhanced transcription of interleukin-6 and fibroblast growth factor-2, genes encoding two important proinflammatory cytokines implicated in the molecular mechanisms of chemoresistance of prostate cancer and its ability to metastasize. The possible roles of reactive oxygen species and impaired mitochondrial oxidation in the prostate cancer cell line are discussed as factors promoting the early stages of C. trachomatis growth in CWR-R1 cells.

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Section: Resultsmentioning

confidence: 99%

Chlamydia trachomatis Growth and Cytokine mRNA Response in a Prostate Cancer Cell Line

Petyaev

Zigangirova

Morgunova

et al. 2019

Advances in Urology

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“…When the sensitivity of a first‐line drug, azithromycin, was examined in C. pneumoniae ‐infected cells, the hypoxic condition significantly decreased the effects of this drug against C. pneumoniae . Interestingly, the antibacterial effect of IFN‐γ, which plays a central role in protective immunity against Chlamydia , was also impaired by reduced phosphorylation of the transcription factor Stat‐1 under hypoxic conditions , suggesting that effects of antibacterial cytokines and antibiotics may be dampened under hypoxia. Although the exact reasons remain unknown, multidrug resistance protein 1 and multidrug resistance‐associated protein 1, which are upregulated by stabilized HIF‐1 under hypoxic conditions, may be involved in reducing antibacterial effects .…”

Section: Discussionmentioning

confidence: 99%

Chlamydia pneumoniae enhances Interleukin 8 (IL‐8) production with reduced azithromycin sensitivity under hypoxia

Matsuo

Sakai

Okubo

et al. 2019

APMIS

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Japan Matsuo J, Sakai K, Okubo T, Yamaguchi H. Chlamydia pneumoniae enhances Interleukin 8 (IL-8) production with reduced azithromycin sensitivity under hypoxia. APMIS 2019; 127: 131-138.Obligate intracellular bacterium Chlamydia pneumoniae causes respiratory tract infections such as community-acquired pneumonia. During infection, C. pneumoniae induces inflammatory responses in host cells and the oxygen concentration at the infection sites subsequently decreases. Because hypoxic conditions influence further inflammatory responses and reduced antibacterial effects, this may exacerbate the C. pneumoniae infection. Here, we show inflammatory responses and drug sensitivity in C. pneumoniae-infected cells under hypoxic conditions. First, we confirmed the enhanced growth of C. pneumoniae under hypoxia, which indicates that the hypoxic condition we used could adequately reproduce past reports. We then demonstrated a significant increase in production of the pro-inflammatory cytokine Interleukin 8 (IL-8) in C. pneumoniae-infected cells under hypoxic conditions. Furthermore, hypoxia decreased the antibacterial effects of azithromycin against C. pneumoniae compared with normoxic conditions. Together, our data suggest that inflammatory responses and drug sensitivity may have been underestimated in C. pneumoniae infection in previous studies. Thus, to accurately understand the Chlamydia infection, it may be necessary to perform in vitro experiments under hypoxic conditions.

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“…For instance, C. trachomatis and C. pneumoniae can manipulate polyamine and NO synthesis pathways (Caldwell et al, 2003; Abu-Lubad et al, 2014) by promoting ornithine decarboxylase (ODC) expression and reducing iNOS levels. Hypoxia was also reported to reduce the anti-microbial activity of IFN-γ in the context of persistent C. trachomatis infection, indicating that the anti-chlamydial activity of IFN-γ is reduced in the low-oxygen environment that is typical of genital C. trachomatis infections (Jerchel et al, 2014). However, the precise molecular mechanisms remain unknown.…”

Section: Subversion Of the Host Innate Immune Response By Chlamydiamentioning

confidence: 99%

Clear Victory for Chlamydia: The Subversion of Host Innate Immunity

Chen

Wen

2019

Front. Microbiol.

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As obligate intracellular bacterial pathogens, members of the Chlamydia genera are the pivotal triggers for a wide range of infections, which can lead to blinding trachoma, pelvic inflammation, and respiratory diseases. Because of their restricted parasitism inside eukaryotic cells, the pathogens have to develop multiple strategies for adaptation with the hostile intracellular environment—intrinsically present in all host cells—to survive. The strategies that are brought into play at different stages of chlamydial development mainly involve interfering with diverse innate immune responses, such as innate immune recognition, inflammation, apoptosis, autophagy, as well as the manipulation of innate immune cells to serve as potential niches for chlamydial replication. This review will focus on the innate immune responses against chlamydial infection, highlighting the underlying molecular mechanisms used by the Chlamydia spp. to counteract host innate immune defenses. Insights into these subtle pathogenic mechanisms not only provide a rationale for the augmentation of immune responses against chlamydial infection but also open avenues for further investigation of the molecular mechanisms driving the survival of these clinically important pathogens in host innate immunity.

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Host immune responses after hypoxic reactivation of IFN-Î³ induced persistent Chlamydia trachomatis infection

Cited by 17 publications

References 44 publications

Chlamydia trachomatis Growth and Cytokine mRNA Response in a Prostate Cancer Cell Line

Chlamydia trachomatis Growth and Cytokine mRNA Response in a Prostate Cancer Cell Line

Chlamydia pneumoniae enhances Interleukin 8 (IL‐8) production with reduced azithromycin sensitivity under hypoxia

Clear Victory for Chlamydia: The Subversion of Host Innate Immunity

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