Local Host Response to Chlamydial Urethral Infection in Male Guinea Pigs

Wang, Yin; Nagarajan, Uma M.; Hennings, Leah; Bowlin, Anne K.; Rank, Roger G.

doi:10.1128/iai.01339-09

Cited by 23 publications

(18 citation statements)

References 28 publications

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“…Fold induction of mRNA was determined from the threshold cycle (C T ) values normalized for guinea pig ␤-actin expression and then normalized to the value derived from conjunctivae of healthy, uninfected guinea pigs. Primer sequences for gamma interferon (IFN-␥), interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-␣), CCL2 (MCP-1), and CCL5 (RANTES) were published by Wang et al (15). All primers were synthesized by IDT, Inc. (Coralville, IA).…”

Section: Methodsmentioning

confidence: 99%

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Effect of Inflammatory Response on In Vivo Competition between Two Chlamydial Variants in the Guinea Pig Model of Inclusion Conjunctivitis

et al. 2012

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In order to study the interaction of variants in in vivo infection, we employed an azithromycin-resistant mutant (AZ 2 ) and its wild-type parent (SP 6 ) in the guinea pig model of Chlamydia caviae conjunctival infection. When each strain was inoculated individually into conjunctiva, both attained the same level of growth, but AZ 2 elicited less pathology. However, when equal numbers of the two strains were inoculated together into the guinea pig conjunctiva, SP 6 produced a significantly greater number of inclusion-forming units than AZ 2 , and the pathology reflected that of a SP 6 monoinfection. The goal of this study was to further characterize the dynamics of concomitant infection of these two distinct variants, with particular emphasis on the impact of the host response on the in vivo growth of each organism and the development of pathology. Animals infected with AZ 2 had reduced conjunctival infiltration with CD45 ؉ cells and neutrophils as well as a reduced interleukin-8 (IL-8) response. Gene expression of gamma interferon (IFN-␥), tumor necrosis factor alpha (TNF-␣), CCL2, and CCL5 was also significantly lower in AZ 2 -infected animals. The lower inflammatory response induced by AZ 2 was associated with its decreased ability to activate NF-B via Tolllike receptor 2 (TLR2). In general, the inflammatory response in animals infected with both variants was greater than in infection with AZ 2 alone, resulting in lower numbers of AZ 2 than those of SP 6 in the mixed infection. Our results suggest that the ability to elicit an inflammatory response is an important factor in the dynamics of mixed infection with strains that display different pathological phenotypes.

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Section: Methodsmentioning

confidence: 99%

“…For analysis of the numbers and types of lymphocytes present, infected conjunctivae were harvested and processed individually to produce a single-cell suspension as described previously (15). The entire upper conjunctiva from one eye was used to prepare the suspension.…”

Section: Methodsmentioning

confidence: 99%

Effect of Inflammatory Response on In Vivo Competition between Two Chlamydial Variants in the Guinea Pig Model of Inclusion Conjunctivitis

et al. 2012

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“…For analysis of numbers and types of lymphocytes present, infected conjunctivae were harvested and processed individually to produce a single-cell suspension as described previously (47). Approximately, 1 ϫ 10 5 to 2 ϫ 10 5 cells were stained for individual cell surface markers or isotype controls (5 g/ml) for 20 min on ice.…”

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confidence: 99%

“…The RNA samples were then converted into cDNA using oligo(dT), random hexamer primers, and the SuperScript III reverse transcriptase kit from Invitrogen Life Technologies according to the manufacturer's recommendations. Realtime PCR was performed using iQ SYBR green supermix (Bio-Rad Laboratories, Inc., Hercules, CA) in a Bio-Rad iCycler, as described previously (47). No-template controls and DNA melting curve analysis were used as controls to ensure the lack of contaminating DNA in the RNA preparations and to rule out primer-dimer formation, respectively.…”

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Essential Role for Neutrophils in Pathogenesis and Adaptive Immunity in Chlamydia caviae Ocular Infections

et al. 2011

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Trachoma, the world's leading cause of preventable blindness, is produced by chronic ocular infection with Chlamydia trachomatis, an obligate intracellular bacterium. While many studies have focused on immune mechanisms for trachoma during chronic stages of infection, less research has targeted immune mechanisms in primary ocular infections, events that could impact chronic responses. The goal of this study was to investigate the function of neutrophils during primary chlamydial ocular infection by using the guinea pig model of Chlamydia caviae inclusion conjunctivitis. We hypothesized that neutrophils help modulate the adaptive response and promote host tissue damage. To test these hypotheses, guinea pigs with primary C. caviae ocular infections were depleted of neutrophils by using rabbit antineutrophil antiserum, and immune responses and immunopathology were evaluated during the first 7 days of infection. Results showed that neutrophil depletion dramatically decreased ocular pathology, both clinically and histologically. The adaptive response was also altered, with increased C. caviae-specific IgA titers in tears and serum and decreased numbers of CD4 ؉ and CD8 ؉ T cells in infected conjunctivae. Additionally, there were changes in conjunctival chemokines and cytokines, such as increased expression of IgA-promoting interleukin-5 and anti-inflammatory transforming growth factor ␤, along with decreased expression of T cell-recruiting CCL5 (RANTES). This study, the first to investigate the role of neutrophils in primary chlamydial ocular infection, indicates a previously unappreciated role for neutrophils in modulating the adaptive response and suggests a prominent role for neutrophils in chlamydia-associated ocular pathology.

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“…For analysis of numbers and phenotypes of leukocytes present, cervices and uterine horns were harvested and processed individually to produce a single-cell suspension as described previously (13). The entire cervix and a 0.5-cm section of uterine horn were used to prepare the suspension.…”

Section: Methodsmentioning

confidence: 99%

Chlamydial Variants Differ in Ability To Ascend the Genital Tract in the Guinea Pig Model of Chlamydial Genital Infection

et al. 2015

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An important question in the study of chlamydial genital tract disease is why some women develop severe upper tract disease while others have mild or even "silent" infections with or without pathology. Animal studies suggest that the pathological outcome of an infection is dependent upon both the composition of the infecting chlamydial population and the genotype of the host, along with host physiological effects, such as the cyclical production of reproductive hormones and even the size of the infecting inoculum or the number of repeated infections. In this study, we compared two variants of Chlamydia caviae, contrasting in virulence, with respect to their abilities to ascend the guinea pig genital tract. We then determined the effect of combining the two variants on the course of infection and on the bacterial loads of the two variants in the genital tract. Although the variants individually had similar infection kinetics in the cervix, SP6, the virulent variant, could be isolated from the oviducts more often and in greater numbers than the attenuated variant, AZ2. SP6 also elicited higher levels of interleukin 8 (IL-8) in the lower genital tract and increased leukocyte infiltration in the cervix and uterus compared to AZ2. When the two variants were combined in a mixed infection, SP6 outcompeted AZ2 in the lower genital tract; however, AZ2 was able to ascend the genital tract as readily as SP6. These data suggest that the ability of SP6 to elicit an inflammatory response in the lower genital tract facilitates the spread of both variants to the oviducts.

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Local Host Response to Chlamydial Urethral Infection in Male Guinea Pigs

Cited by 23 publications

References 28 publications

Effect of Inflammatory Response on In Vivo Competition between Two Chlamydial Variants in the Guinea Pig Model of Inclusion Conjunctivitis

Effect of Inflammatory Response on In Vivo Competition between Two Chlamydial Variants in the Guinea Pig Model of Inclusion Conjunctivitis

Essential Role for Neutrophils in Pathogenesis and Adaptive Immunity in Chlamydia caviae Ocular Infections

Chlamydial Variants Differ in Ability To Ascend the Genital Tract in the Guinea Pig Model of Chlamydial Genital Infection

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