Early Colonization of the Upper Genital Tract by Chlamydia muridarum Is Associated with Enhanced Inflammation Later in Infection

Helble, Jennifer D.; Reinhold-Larsson, Nicole; Starnbach, Michael N.

doi:10.1128/iai.00405-19

Cited by 4 publications

(4 citation statements)

References 28 publications

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“…Future work will address whether or not this is an NR1 or transcervical inoculation-specific phenomenon within the context of Chlamydia infection. Indeed, transcervical inoculation and intravaginal inoculation with C. muridarum elicit different immune responses in the upper genital tract (21), and future work will determine if the inflammatory sections in the upper genital tract that occur with C. trachomatis transcervical inoculation also occur with C. muridarum intravaginal inoculation following ascension.…”

Section: Discussionmentioning

confidence: 99%

Gamma Interferon Is Required forChlamydiaClearance but Is Dispensable for T Cell Homing to the Genital Tract

Helble

González

Andrian

et al. 2020

mBio

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While there is no effective vaccine against Chlamydia trachomatis infection, previous work has demonstrated the importance of C. trachomatis-specific CD4+ T cells (NR1 T cells) in pathogen clearance. Specifically, NR1 T cells have been shown to be protective in mice, and this protection depends on the host’s ability to sense the cytokine gamma interferon (IFN-γ). However, it is unclear what role NR1 production or sensing of IFN-γ plays in T cell homing to the genital tract or T cell-mediated protection against C. trachomatis. Using two-photon microscopy and flow cytometry, we found that naive wild-type (WT), IFN-γ−/−, and IFN-γR−/− NR1 T cells specifically home to sections in the genital tract that contain C. trachomatis. We also determined that protection against infection requires production of IFN-γ from either NR1 T cells or endogenous cells, further highlighting the importance of IFN-γ in clearing C. trachomatis infection. IMPORTANCE Chlamydia trachomatis is an important mucosal pathogen that is the leading cause of sexually transmitted bacterial infections in the United States. Despite this, there is no vaccine currently available. In order to develop such a vaccine, it is necessary to understand the components of the immune response that can lead to protection against this pathogen. It is well known that antigen-specific CD4+ T cells are critical for Chlamydia clearance, but the contexts in which they are protective or not protective are unknown. Here, we aimed to characterize the importance of gamma interferon production and sensing by T cells and the effects on the immune response to C. trachomatis. Our work here helps to define the contexts in which antigen-specific T cells can be protective, which is critical to our ability to design an effective and protective vaccine against C. trachomatis.

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Section: Discussionmentioning

confidence: 99%

Gamma Interferon Is Required forChlamydiaClearance but Is Dispensable for T Cell Homing to the Genital Tract

Helble

González

Andrian

et al. 2020

mBio

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“…The inability to ascend in the mouse female reproductive tract could indicate an inability to replicate or establish a niche within the endometrial tissues. Therefore, transcervical infection was conducted by infecting the bacteria directly into the uterine horns using an implantation device to bypass the cervix (Helble et al, 2019).…”

Section: Pz Chimeras Exhibit Infection Capabilities Similar To C Trachomatis In the Mouse Modelmentioning

confidence: 99%

Inter‐species lateral gene transfer focused on the Chlamydia plasticity zone identifies loci associated with immediate cytotoxicity and inclusion stability

Dimond

Suchland

Baid

et al. 2021

Molecular Microbiology

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Chlamydia muridarum actively grows in murine mucosae and is a representative model of human chlamydial genital tract disease. In contrast, C. trachomatis infections in mice are limited and rarely cause disease. The factors that contribute to these differences in host adaptation and specificity remain elusive. Overall genomic similarity leads to challenges in the understanding of these significant differences in tropism. A region of major genetic divergence termed the plasticity zone (PZ) has been hypothesized to contribute to the host specificity. To evaluate this hypothesis, lateral gene transfer was used to generate multiple hetero-genomic strains that are predominately C. trachomatis but have replaced regions of the PZ with those from C. muridarum. In vitro analysis of these chimeras revealed C. trachomatis-like growth as well as poor mouse infection capabilities. Growth-independent cytotoxicity phenotypes have been ascribed to three large putative cytotoxins (LCT) encoded in the C. muridarum PZ. However, analysis of PZ chimeras supported that gene products other than the LCTs are responsible for cytopathic and cytotoxic phenotypes. Growth analysis of associated chimeras also led to the discovery of an inclusion protein, CTL0402 (CT147), and homolog TC0424, which was critical for the integrity of the inclusion and preventing apoptosis.

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“…C. muridarum-dsRed transformation and plaque purification was then performed as described previously 92 . C. muridarum-dsRed was propagated in McCoy cells using 500 µg/ml spectinomycin and elementary bodies (EBs) isolated as previously described [93][94][95] . Aliquots of purified EBs were stored at -80°C in SPG buffer containing 250 mM sucrose, 10 mM sodium phosphate, and 5mM L-glutamic acid and thawed immediately prior to use.…”

Section: Pathogensmentioning

confidence: 99%

Constitutive immune surveillance of nasal mucosa by three neutrophil subsets with distinct origin, phenotype, and function

Gonzalez,

Hanč,

Alvarez

et al. 2024

Preprint

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The nasal mucosa (NM) has several critical functions, including as a chemosensory organ, as a filter and conditioning surface of inhaled air for the lower airways, and as a first line of defense against airborne infections. Owing to its constant exposure to ever-changing environments, the NM is arguably the most frequently infected tissue in mammals. Consequently, vertebrates harbor an intricate network of subepithelial immune cells that are dispersed throughout the NM. However, the origin, composition, and function of nasal immune cells and their pathophysiological role are poorly understood. Here, we show that murine steady-state NM harbors a prominent population of extravascular neutrophils (EVN) that are abundant in both conventional and germ-free mice, suggesting that their presence is not driven by microbial stimuli. Nasal EVN can be subdivided into three phenotypically distinct subsets: one population that we have termed nN1 is CD11bintLy6Gint, while the other two subsets are both CD11bhiLy6Ghiand distinguishable by the absence (nN2) or presence (nN3) of CD11c and SiglecF. nN1 EVN originate in bone marrow (BM) within osseous structures in the skull. These locally produced neutrophils appear to access the adjacent NM via conduits that connect BM cavities to the submucosal lamina propria. nN2 cells reach the NM via the blood and readily engulf infectious microbes. In the absence of infection, nN2 cells differentiate into the nN3 subset, which does not capture microbes but assumes phenotypic and functional features of antigen-presenting cells, including the capacity to cross-present exogenous antigens to CD8 T cells. These findings indicate that steady-state mammalian NM harbors a unique innate cellular immune environment that is unlike any other barrier tissue.

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Early Colonization of the Upper Genital Tract by Chlamydia muridarum Is Associated with Enhanced Inflammation Later in Infection

Cited by 4 publications

References 28 publications

Gamma Interferon Is Required forChlamydiaClearance but Is Dispensable for T Cell Homing to the Genital Tract

Gamma Interferon Is Required forChlamydiaClearance but Is Dispensable for T Cell Homing to the Genital Tract

Inter‐species lateral gene transfer focused on the Chlamydia plasticity zone identifies loci associated with immediate cytotoxicity and inclusion stability

Constitutive immune surveillance of nasal mucosa by three neutrophil subsets with distinct origin, phenotype, and function

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