The protective efficacy of chlamydial protease-like activity factor vaccination is dependent upon CD4+ T cells

Murphey, Cathi; Murthy, Ashlesh K.; Meier, Patricia A.; Guentzel, M. Neal; Zhong, Guangming; Arulanandam, Bernard P.

doi:10.1016/j.cellimm.2006.10.002

Cited by 50 publications

(62 citation statements)

References 25 publications

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“…5), because this is a most commonly used method for monitoring chlamydial infection in mice (35,40,49). MyD88 KO mice only displayed a slightly increased shedding intensity and duration, which is consistent with a previous observation (35) but still surprising to us given the severe deficiency in early inflammation and the strongly Th2-biased adaptive response in the MyD88 KO mice.…”

Section: Deficiency In Myd88 Allows Chlamydial Organisms To Ascend Insupporting

confidence: 88%

Mice Deficient in MyD88 Develop a Th2-Dominant Response and Severe Pathology in the Upper Genital Tract following Chlamydia muridarum Infection

Chen

Lei

Chang

et al. 2010

The Journal of Immunology

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110

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MyD88, a key adaptor molecule required for many innate immunity receptor-activated signaling pathways, was evaluated in a Chlamydia muridarum urogenital tract infection model. Compared with wild-type mice, MyD88 knockout (KO) mice failed to produce significant levels of inflammatory cytokines in the genital tract during the first week of chlamydial infection. MyD88 KO mice developed a Th2-dominant whereas wild-type mice developed a Th1/Th17-dominant immune response after chlamydial infection. Despite the insufficient production of early inflammatory cytokines and lack of Th1/Th17-dominant adaptive immunity, MyD88 KO mice appeared to be as resistant to chlamydial intravaginal infection as wild-type mice based on the number of live organisms recovered from vaginal samples. However, significantly high numbers of chlamydial organisms were detected in the upper genital tract tissues of MyD88 KO mice. Consequently, MyD88 KO mice developed more severe pathology in the upper genital tract. These results together have demonstrated that MyD88-dependent signaling pathway is not only required for inflammatory cytokine production in the early phase of host response to chlamydial infection but also plays a critical role in the development of Th1/Th17 adaptive immunity, both of which may be essential for limiting ascending infection and reducing pathology of the upper genital tract by chlamydial organisms.

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Section: Deficiency In Myd88 Allows Chlamydial Organisms To Ascend Insupporting

confidence: 88%

Mice Deficient in MyD88 Develop a Th2-Dominant Response and Severe Pathology in the Upper Genital Tract following Chlamydia muridarum Infection

Chen

Lei

Chang

et al. 2010

The Journal of Immunology

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110

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“…We and others have identified a number of other C. trachomatis-specific CD4 + and CD8 + T-cell antigens from Chlamydia-infected mice using a variety of approaches (Allen et al, 1991;Beatty and Stephens, 1992;Ishizaki et al, 1992;Su et al, 1990;Murphey et al, 2006;and our unpub. data).…”

Section: Immune-mediated Control Of Chlamydia Infection 13mentioning

confidence: 89%

Immune-mediated control of Chlamydia infection

Roan

Starnbach²

2007

Cell Microbiol

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SummaryInfection with the bacterium Chlamydia trachomatis can lead to a variety of diseases, including ectopic pregnancy, infertility and blindness. Exposure of the host to C. trachomatis stimulates multiple innate and adaptive immune effectors that can contribute towards controlling bacterial replication. However, these effectors are often insufficient to resolve the infection and prevent re-infection, and the continued presence of C. trachomatis within the host may induce immune effectors to chronically produce inflammatory cytokines. This may eventually lead to the tissue pathologies associated with the infection. Reducing the incidence and sequelae of infection will ultimately require the development of a C. trachomatis vaccine that can stimulate sterilizing immunity while avoiding immune-mediated pathology.

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“…The major outer membrane protein (MOMP) and the outer membrane protein 2 (OMP2) are quantitatively dominant Chlamydia membrane proteins and MOMP in particular is known to contain both class I and class II T cell epitopes. Other Chlamydia proteins containing T cell Ags comprise both cytoplasmic and membrane proteins and include: heat shock protein 60 (Hsp60), homolog of Yersinia pseudotuberculosis YopD (YopD), enolase, polymorphic membrane protein D (PmpD), and Chlamydia protease-like activity factor (CPAF) (6,36).…”

Section: Discussionmentioning

confidence: 99%

Immunoproteomic Discovery of Novel T Cell Antigens from the Obligate Intracellular PathogenChlamydia

Karunakaran

Rey-Ladino

Stoynov

et al. 2008

The Journal of Immunology

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*Chlamydia infections cause substantial morbidity worldwide and effective prevention will depend on a vaccine. Since Chlamydia immunity is T cell-mediated, a major impediment to developing a molecular vaccine has been the difficulty in identifying relevant T cell Ags. In this study, we used a combination of affinity chromatography and tandem mass spectrometry to identify 13 Chlamydia peptides among 331 self-peptides presented by MHC class II (I-A b ) molecules from bone marrow-derived murine dendritic cells infected with Chlamydia muridarum. These MHC class II-bound peptides were recognized by Chlamydia-specific CD4 T cells harvested from immune mice and adoptive transfer of dendritic cells pulsed ex vivo with the peptides partially protected mice against intranasal and genital tract Chlamydia infection. The results provide evidence for lead vaccine candidates for a T cell-based subunit molecular vaccine against Chlamydia infection suitable for human study. The Journal of Immunology, 2008, 180: 2459 -2465. W orld-wide Chlamydia trachomatis is annually responsible for Ͼ92 million sexually transmitted infections and 85 million ocular infections (1). Public health programs have targeted C. trachomatis as a major problem because the organism causes long-term sequelae such as infertility, ectopic pregnancy, and blindness. Sexually transmitted C. trachomatis is also a potent cofactor facilitating the transmission of HIV (2) and interacts with oncogenic human papilloma virus in the pathogenesis of cervical neoplasia (3). In developed countries, public health measures to control Chlamydia are failing as case rates continue to rise, perhaps due to early antibiotic treatment interfering with the acquisition of immunity (4); these approaches to control Chlamydia are not feasible for much of the developing world. Thus, a new approach, such as an effective vaccine, is needed if Chlamydia control is to be achieved in the developing and developed world.Previous vaccine research using inactivated Chlamydia bacterial cells demonstrated partial short-term protection which may have been complicated by immunopathology during breakthrough infection (5). These vaccine trials yielded important lessons for the modern era of Chlamydia vaccinology, namely, that an effective Chlamydia vaccine will need to be molecularly defined and engender long-lived protective immune responses. Immunity to C. trachomatis is now known to depend on cell-mediated immune (CMI) 3 responses, especially Th1-polarized cytokine responses (6). Abs appear to play a secondary role (7). Experience has shown that developing vaccines for intracellular pathogens that require protective CMI is more difficult than for pathogens that simply require protective Ab (8). Part of the problem has been the identification of Ags that induce CMI responses because such Ags need to be presented to T cells by MHC molecules, and identifying MHC-bound microbial epitopes has been notoriously difficult (6). Since T cell responses mainly recognize protein Ags, protective vaccine candida...

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The protective efficacy of chlamydial protease-like activity factor vaccination is dependent upon CD4+ T cells

Cited by 50 publications

References 25 publications

Mice Deficient in MyD88 Develop a Th2-Dominant Response and Severe Pathology in the Upper Genital Tract following Chlamydia muridarum Infection

Mice Deficient in MyD88 Develop a Th2-Dominant Response and Severe Pathology in the Upper Genital Tract following Chlamydia muridarum Infection

Immune-mediated control of Chlamydia infection

Immunoproteomic Discovery of Novel T Cell Antigens from the Obligate Intracellular PathogenChlamydia

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