Genetic susceptibility to chlamydial salpingitis and subsequent infertility in mice

Tuffrey, Maureen; Alexander, Frances; Woods, C. A.; Taylor-Robinson, D.

doi:10.1530/jrf.0.0950031

Cited by 47 publications

(49 citation statements)

References 7 publications

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“…For example, there is variability among several inbred strains in susceptibility to genital tract infection with serovars of C. trachomatis. [11][12][13][14][15][16] Recent experiments with the mouse pneumonitis (MoPn) biovar of C. trachomatis have demonstrated that this variability is partly related to the cytokine profile in the genital tract during infection. C57BL/6 mice, which exhibit relatively mild pathological outcomes when compared to BALB/c or C3H/HeN mice, seem to have a more vigorous Th1 response with higher levels of tumor necrosis factor-a, interferon-g, and macrophage inflammatory protein-1a.…”

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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Section: Introductionmentioning

confidence: 99%

Genetic analysis of susceptibility to Chlamydia trachomatis in mouse

et al. 2006

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“…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 C57BL/6 (H-2 b ), BALB/c (H-2 d ), C3H/HeN (H-2 k ), and DBA/2J (H-2 d ) mice respond to respiratory (1,39,40,63), genital (9)(10)(11)(12)52), and intraperitoneal (i.p.) (36) Chlamydia infections differently.…”

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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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“…Genetically controlled differences in susceptibility to primary chlamydial infection have been observed among inbred mouse strains (9,27,29). Data reported by de le Maza et al (9) revealed the development of higher degrees of infertility in C3H/HeN (C3H) and BALB/c mice than in C57BL/6 (C57) mice after intravaginal inoculation of MoPn.…”

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confidence: 99%

Early Local Cytokine Profiles in Strains of Mice with Different Outcomes from Chlamydial Genital Tract Infection

et al. 2001

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In this study, we expand on the examination of genetically determined differences in host responses that correlate with clearance of Chlamydia trachomatis from the genital tract. We infected C57BL/6, BALB/c, and C3H/HeN mice with the mouse pneumonitis agent of C. trachomatis (MoPn). C57BL/6 mice had the shortest course of infection (22 days) and the lowest incidence of severe hydrosalpinx. BALB/c mice also had a short course of infection (25 days), but all developed hydrosalpinx. C3H/HeN mice had the longest course of infection (38 days), and all developed severe hydrosalpinx. Determination of local cytokine responses by enzyme-linked immunosorbent assay (ELISA) of genital tract secretions revealed that the levels of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-␣) and interleukin-1␤ (IL-1␤) were significantly increased in the C57BL/6 and BALB/c strains compared to those in the C3H/HeN strain whereas the level of IL-6 was not different. The level of the neutrophil chemokine macrophage inflammatory protein 2 (MIP-2) was increased during the first week of infection in all three strains but was significantly higher in the BALB/c strain, the strain with the most rapid influx of neutrophils into the genital tract. Prolonged detection of MIP-2 in C3H/HeN mice was associated with a protracted presence of neutrophils in the genital tract. Early increases in the levels of the proinflammatory cytokines TNF-␣ and IL-1␤ are associated with earlier eradication of infection in the C57BL/6 and BALB/c strains than in the C3H/HeN strain. Increased levels of MIP-2 and neutrophils in BALB/c and C3H/HeN mice relative to C57BL/6 mice suggest that these responses may contribute to pathology.

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Genetic susceptibility to chlamydial salpingitis and subsequent infertility in mice

Cited by 47 publications

References 7 publications

Genetic analysis of susceptibility to Chlamydia trachomatis in mouse

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

Early Local Cytokine Profiles in Strains of Mice with Different Outcomes from Chlamydial Genital Tract Infection

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