CD14 promoter polymorphism −159C&gt;T is associated with susceptibility to chronic Chlamydia pneumoniae infection in peripheral blood monocytes

Rupp, Jan; Goepel, Wolfgang; Kramme, Evelyn; Jahn, Jürgen; Solbach, Werner; Maass, Matthias

doi:10.1038/sj.gene.6364112

Cited by 36 publications

(34 citation statements)

References 18 publications

(23 reference statements)

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“…This bears an interesting relationship to our findings in the present study, in which as-yetuncharacterized genetic susceptibility conferring sensitivity to experimental C trachomatis-induced arthritis was also associated with a relative lack of IFN␥ production locally. A comparable analogy can be seen in the significant associations observed between low TNF␣ secretion and a more chronic course of ReA in HLA-B27-positive patients, but that is not always the case (47,42). This also could represent the clinical parallel to that seen in the current study, in which relatively impaired host TNF␣ production was associated with the chronicity and severity of the experimental C trachomatis-induced arthritis.…”

Section: Host-microbe Interactions In Chlamydia-induced Arthritissupporting

confidence: 70%

“…Netea et al reported that Chlamydia pneumoniae stimulates IFN␥ synthesis through MyD88-dependent, Toll-like receptor 2 (TLR-2)-and TLR-4-independent induction of IL-18 release (46). Polymorphisms in CD14 may confer differential host responsiveness to chlamydia (47). Eng et al recently reported a CD14 promoter polymorphism associated with CD14 expression and Chlamydia-stimulated TNF␣ production (48).…”

Section: Host-microbe Interactions In Chlamydia-induced Arthritismentioning

confidence: 99%

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Early cytokine profiles in the joint define pathogen clearance and severity of arthritis in Chlamydia‐induced arthritis in rats

Inman

Chiu

2006

Arthritis & Rheumatism

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Objective. Although Chlamydia trachomatisinduced arthritis is among the most common rheumatic diseases having an identified infectious trigger, the pathogenesis of this arthritis is not well defined. We sought to investigate the host-microbe interactions that contribute to the severity of arthritis initiated by chlamydial infection.Methods. We established an experimental rat model of C trachomatis-induced arthritis that recapitulates many pathologic features of the clinical disease. The severity of the arthritis was defined using an established histopathologic scoring system. Host clearance of the pathogen and local cytokine production were examined by enzyme-linked immunosorbent assays.Results. Lewis rats were susceptible to C trachomatis-induced arthritis, whereas BN rats were relatively resistant to this disease. Significant differences in the histopathologic severity of arthritis were originally observed on day 21, and this prompted an examination of the acute phase of the arthritis. As early as day 5 after the onset of the arthritis, pathologic changes in Lewis rats were more severe than those in BN rats. An evaluation of the role of complement using cobra venom factor treatment excluded complement as being the key to differential sensitivity, because decomplementation did not eliminate the differences in arthritis severity between Lewis and BN rats. Host clearance, in contrast, was significantly different between the rat strains, with BN rats showing more prompt and effective clearance of the pathogen from both synovial tissues and spleen compared with Lewis rats. Local cytokine profiles demonstrated that host resistance was characterized by enhanced synovial expression of tumor necrosis factor ␣, interferon-␥ (IFN␥), and interleukin-4.Conclusion. These studies demonstrated that cytokines thought to be proinflammatory in nature can play an important role in host defense in infectiontriggered arthritis and serve to highlight the dynamic cytokine relationships that constitute effective hostpathogen interactions.

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Section: Host-microbe Interactions In Chlamydia-induced Arthritissupporting

confidence: 70%

Section: Host-microbe Interactions In Chlamydia-induced Arthritismentioning

confidence: 99%

Early cytokine profiles in the joint define pathogen clearance and severity of arthritis in Chlamydia‐induced arthritis in rats

Inman

Chiu

2006

Arthritis & Rheumatism

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“…3,4 Host genetic factors likely play an important role in this variability, and indeed, human genetic studies have shown associations between increased prevalence or severity of Chlamydia infection and certain human leukocyte antigen haplotypes [5][6][7][8] or polymorphisms in CD-14, tumor necrosis factor-a, or interleukin-10. [8][9][10] Although these reports show associations that are likely to be relevant, it is difficult to confirm their biological significance using human studies.…”

Section: Introductionmentioning

confidence: 99%

Genetic analysis of susceptibility to Chlamydia trachomatis in mouse

et al. 2006

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Chlamydia trachomatis is a bacterial pathogen that is a major cause of blindness and infertility in diverse populations across the world. In an effort to model genetic complexities that are observed in human populations and to identify novel genes involved in susceptibility to C. trachomatis, we have adapted a murine model of systemic infection for use in genetic analysis. In this model, chlamydial colonization and replication is measured in the spleens of mice shortly after intravenous delivery of C. trachomatis L2. Here, we show that C57BL/6J and C3H/HeJ inbred mice are differentially susceptible to this systemic infection. Additionally, fibroblasts cultured from C57BL/6J and C3H/HeJ embryos are differentially permissive for chlamydial replication. We have taken advantage of this natural variation to map quantitative trait loci on Chromosomes 2, 3, and 11 that segregate with the bacterial load in F2 cross progeny during the acute phase of C. trachomatis infection in vivo. To validate our mapping results, we also generated mice that are congenic for a portion of Chromosome 11 from the susceptible parent. This congenic interval confers increased susceptibility to C. trachomatis, both in vivo and in vitro, suggesting that our screen identified at least one gene that is involved in cellular resistance to C. trachomatis replication.

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“…Host genetic factors appear to be important in determining the outcome of Chlamydia infections. It has been reported that the increased incidence of Chlamydia-induced chronic diseases, such as tubal infertility and scarring trachoma, is correlated with certain human leukocyte antigen (HLA) haplotypes and polymorphism of genes encoding interleukin-10 (IL-10), CD14, and tumor necrosis factor alpha (6,7,16,25,44,54). However, how these specific genes are involved in shaping the specific immune responses during Chlamydia infection in humans remains unclear.…”

mentioning

confidence: 99%

Critical Role of the Interleukin-17/Interleukin-17 Receptor Axis in Regulating Host Susceptibility to Respiratory Infection withChlamydiaSpecies

Zhou¹,

Chen²,

Moore³

et al. 2009

Infect Immun

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The specific contribution of interleukin-17/interleukin-17 receptor (IL-17/IL-17R)-mediated responses in regulating host susceptibility against obligatory intracellular Chlamydia infection was investigated in C57BL/6 and C3H/HeN mice during Chlamydia muridarum respiratory infection. We demonstrated that Chlamydia stimulated IL-17/IL-17R-associated responses in both Chlamydia-resistant C57BL/6 and Chlamydia-susceptible C3H/HeN mice. However, C3H/HeN mice developed a significantly greater IL-17/IL-17R-associated response than C57BL/6 mice did. This was reflected by an increase in IL-17 mRNA expression, a higher recall IL-17 production from splenocytes upon antigen restimulation, and higher production of Chlamydia trachomatis is an obligate intracellular gram-negative bacterium that primarily infects epithelial cells lining the ocular, respiratory, and urogenital tract surfaces and causes many human diseases including trachoma, pneumonia, and pelvic inflammatory disease (2). Although effective antibiotics are available, the incidence of C. trachomatis infections continues to increase worldwide (41). In the United States alone, it is estimated that there are approximately 2.8 million new cases of urogenital C. trachomatis infection each year (58). An effective and safe Chlamydia vaccine is needed to address the global C. trachomatis epidemic, and a comprehensive understanding of the means of protective immunity and immunopathology of C. trachomatis infection is essential for vaccine development.C. trachomatis infection results in a wide variety of clinical manifestations, ranging from asymptomatic to mild or severe symptoms, acute or chronic inflammatory responses, and a wide range of chronic complications (5,47,59). Host genetic factors appear to be important in determining the outcome of Chlamydia infections. It has been reported that the increased incidence of Chlamydia-induced chronic diseases, such as tubal infertility and scarring trachoma, is correlated with certain human leukocyte antigen (HLA) haplotypes and polymorphism of genes encoding interleukin-10 (IL-10), CD14, and tumor necrosis factor alpha (6,7,16,25,44,54). However, how these specific genes are involved in shaping the specific immune responses during Chlamydia infection in humans remains unclear. As in humans, inbred mouse strains, such as, and DBA/2J (H-2 d ) mice respond to respiratory (1,39,40,63), genital (9-12, 52), and intraperitoneal (i.p.) (36) Chlamydia infections differently. C57BL/6 mice are regarded as a resistant strain, whereas BALB/c, DBA/2, and C3H/HeN mice are reported as susceptible strains with higher mortality, more prolonged bacterial burden, more severe tissue inflammatory responses (such as neutrophil infiltration), and higher rates of infertility following Chlamydia infection. Thus, these inbred mouse strains have been used extensively for identification of specific host factors that regulate immune responses and immune mechanisms underlying the pathogenesis of Chlamydia infection.Based on animal models (5,8,38,50) and hum...

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CD14 promoter polymorphism −159C>T is associated with susceptibility to chronic Chlamydia pneumoniae infection in peripheral blood monocytes

Cited by 36 publications

References 18 publications

Early cytokine profiles in the joint define pathogen clearance and severity of arthritis in Chlamydia‐induced arthritis in rats

Early cytokine profiles in the joint define pathogen clearance and severity of arthritis in Chlamydia‐induced arthritis in rats

Genetic analysis of susceptibility to Chlamydia trachomatis in mouse

Critical Role of the Interleukin-17/Interleukin-17 Receptor Axis in Regulating Host Susceptibility to Respiratory Infection withChlamydiaSpecies

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