T cell responses to Chlamydia trachomatis

Loomis, Wendy P.; Starnbach, Michael N.

doi:10.1016/s1369-5274(02)00291-6

Cited by 101 publications

(76 citation statements)

References 52 publications

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“…Some of the bettercharacterized intracellular defense mechanisms are linked to the release of proinflammatory cytokines that accompanies Chlamydia infection. A key inducer of cellular resistance in this regard is IFN-␥, a cytokine that is released primarily by T cells at the site of Chlamydia infection and that induces intracellular cascades that inhibit Chlamydia replication (15,20).…”

Section: Discussionmentioning

confidence: 99%

The p47 GTPases Igtp and Irgb10 map to the Chlamydia trachomatis susceptibility locus Ctrq-3 and mediate cellular resistance in mice

Bernstein-Hanley

Coers²,

Balsara³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Infections caused by the bacteria Chlamydia trachomatis contribute to diverse pathologies in a variety of human populations. We previously used a systemic model of C. trachomatis infection in mice to map three quantitative trait loci that influence in vivo susceptibility differences between the C57BL͞6J and C3H͞HeJ inbred strains of mouse. One of these quantitative trait loci, Ctrq-3, influences an IFN-␥-dependent susceptibility difference in primary embryonic fibroblasts isolated from these strains. Here we use fine structure mapping in congenic fibroblasts carrying DNA from the susceptible parent to localize the effect of Ctrq-3 to a 1.2-megabase interval of genomic DNA that contains Irgb10 and Igtp, two members of the IFN-␥-inducible p47 family of GTPases. This class of proteins has been widely implicated in resistance to intracellular pathogens in mice. We analyzed expression of Irgb10 and Igtp in parental and congenic embryonic fibroblasts treated with IFN-␥ and found that relatively resistant fibroblasts express more Irgb10 than relatively susceptible fibroblasts. However, we also found that abolishing the expression of either Irgb10 or Igtp increases susceptibility of embryonic fibroblasts to C. trachomatis. Thus, we conclude that, although a difference in Irgb10 expression is likely responsible for the effect of Ctrq-3 on susceptibility to C. trachomatis, both genes play a role in intracellular resistance to C. trachomatis.genetic ͉ infection ͉ mouse ͉ immunity ͉ interferon

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Section: Discussionmentioning

confidence: 99%

The p47 GTPases Igtp and Irgb10 map to the Chlamydia trachomatis susceptibility locus Ctrq-3 and mediate cellular resistance in mice

Bernstein-Hanley

Coers²,

Balsara³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…The development of Chlamydia vaccines have historically been focused on the induction of humoral immunity (2). Recent studies have confirmed the importance of both B and T cells in resolving chlamydial genital infection (38). Chlamydiae are obligate intracellular bacteria that normally infect the single-cell columnar layer of the genital tract epithelia, which express MHC class I molecules.…”

Section: (E and F)mentioning

confidence: 99%

Cleavage of p65/RelA of the NF-κB pathway by Chlamydia

Lad

Correia

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

107

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Chlamydia trachomatis is a bacterial pathogen that infects the eyes and urogenital tract. Ocular infection by this organism is the leading cause of preventable blindness worldwide. The infection is also a leading cause of sexually transmitted disease in the United States. As obligate intracellular pathogens, chlamydiae have evolved sophisticated, yet undefined, mechanisms to maintain a favorable habitat for intracellular growth while avoiding harm to the host. We show here that chlamydiae have the ability to interfere with the NF-B pathway of host inflammatory response. We found that Chlamydia infection did not promote I B␣ degradation, a prerequisite for NF-B nuclear translocation/activation, nor induce p65/RelA nuclear redistribution. Instead, it caused p65 cleavage into an N terminus-derived p40 fragment and a p22 of the C terminus. The activity was specific because no protein cleavage or degradation of NF-B pathway components was detected. Moreover, murine p65 protein was resistant to cleavage by both human and mouse biovars. The chlamydial protein that selectively cleaved p65 was identified as a tail-specific protease (CT441). Importantly, expression of either this protease or the p40 cleavage product could block NF-B activation. A hallmark of chlamydial STD is its asymptomatic nature, although inflammatory cellular response and chronic inflammation are among the underlying mechanisms. The data presented here demonstrate that chlamydiae have the ability to convert a regulatory molecule of host inflammatory response to a dominant negative inhibitor of the same pathway potentially to minimize inflammation.CT441 ͉ inflammation ͉ protease

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“…1,2 As an intracellular pathogen C trachomatis infection induces antigen-specific cell-mediated immune (CMI) response of T-helper cell type 1 (Th1). 3 Th1 cytokines interleukin-12 (IL-12), TNF-a and most notably IFN-g are crucial in resolving primary chlamydial infection. 4 Antigen-specific IFN-g secreting T cells correlate with protection.…”

Section: Introductionmentioning

confidence: 99%

IL-10 polymorphism and cell-mediated immune response to Chlamydia trachomatis

Öhman¹,

Tiitinen

Halttunen

et al. 2006

Genes Immun

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Chlamydia trachomatis infection induces an inflammatory response that is crucial in resolving acute infection but may also play a key role in the pathogenesis of C trachomatis associated infertility. The immune response is linked to cytokine secretion pattern which is influenced by the host genetic background. To study a relationship between interleukin-10 (IL-10) promoter À1082 polymorphism and cell-mediated immune response during C trachomatis infection in vitro, lymphocyte proliferation and cytokine (IL-10, IFN-g, TNF-a, IL-2, IL-4 and IL-5) secretion were analysed in subjects with different IL-10 genotypes. Enhanced IL-10 secretion and reduced antigen-specific lymphocyte proliferative and IFN-g responses were found in subjects with IL-10 À1082 GG genotype when compared to those with À1082 AA genotype. CD14 þ monocytes were main source of IL-10 indicating that these cells are important regulators of the antigen-specific cell-mediated responses during active C trachomatis infection. We conclude that impaired cell-mediated response to C trachomatis is associated with IL-10 genotype in subjects with high IL-10 producing capacity. A comparison of immune markers between subjects with a history of noncomplicated and complicated infection is needed to further understand the confounding factors associated with the development of C trachomatis associated sequelae.

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T cell responses to Chlamydia trachomatis

Cited by 101 publications

References 52 publications

The p47 GTPases Igtp and Irgb10 map to the Chlamydia trachomatis susceptibility locus Ctrq-3 and mediate cellular resistance in mice

The p47 GTPases Igtp and Irgb10 map to the Chlamydia trachomatis susceptibility locus Ctrq-3 and mediate cellular resistance in mice

Cleavage of p65/RelA of the NF-κB pathway by Chlamydia

IL-10 polymorphism and cell-mediated immune response to Chlamydia trachomatis

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