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Alternatively Activated Macrophages Are Host Cells for Chlamydia trachomatis and Reverse Anti-chlamydial Classically Activated Macrophages.

ABSTRACT: The obligate intracellular pathogen Chlamydia trachomatis (Ctr) is the causative agent of the most common form of sexually transmitted disease in the United States. Genital infections with C. trachomatis can lead to inflammatory tissue damage followed by scarring and tissue remodeling during wound healing. Extensive scarring can lead to ectopic pregnancy or infertility. Classically activated macrophages (CA m?), with their anti-microbial effector mechanisms, are known to be involved in acute inflammatory processes during the course of infection. In contrast, alternatively activated macrophages (AA m?) contribute to tissue repair at sites of wound healing, and have reduced bactericidal functions. They are present during infection, and thus potentially can provide a growth niche for C. trachomatis during a course of infection. To address this question, macrophages derived from CD14-positive monocytes magnetically isolated from peripheral blood mononuclear cells (PBMC) were treated with interferon-? or interleukin-4 to produce CA m? or AA m?, respectively. Confocal microscopy of chlamydial inclusions and quantification of infectious yields revealed better pathogen growth and development in AA m? than CA m?, which correlated with the reduced expression of indoleamine 2,3-dioxygenase, a known anti-chlamydial effector of the host. Furthermore, AA m? stained strongly for transferrin receptor and secreted higher amounts of anti-inflammatory interleukin-10 compared to CA m?, characteristics that indicate its suitability as host to C. trachomatis. CA, AA, and resting m? were infected with Ctr serovar L2. The data suggest that IL-10 produced by infected AA m? attenuated the anti-chlamydial function of CA m? with growth recovery observed in infected CA m? in the presence of infected, but not mock-infected AA m?. This could be related to our observation that IL-10 treatment of infected CA m? promoted better chlamydial growth. Thus, in addition to serving as an additional niche, AA m? might also serve as a means to modulate the immediate environment by attenuating the anti-chlamydial functions of nearby CA m? in a manner that could involve IL-10 produced by infected AA m?.

SUBMITTER: Tietzel I

PROVIDER: S-EPMC6524708 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Alternatively Activated Macrophages Are Host Cells for Chlamydia trachomatis and Reverse Anti-chlamydial Classically Activated Macrophages.

Tietzel Illya I Quayle Alison J AJ Carabeo Rey A RA

Frontiers in microbiology 20190507

The obligate intracellular pathogen Chlamydia trachomatis (Ctr) is the causative agent of the most common form of sexually transmitted disease in the United States. Genital infections with C. trachomatis can lead to inflammatory tissue damage followed by scarring and tissue remodeling during wound healing. Extensive scarring can lead to ectopic pregnancy or infertility. Classically activated macrophages (CA mϕ), with their anti-microbial effector mechanisms, are known to be involve ...[more]

PMID: 31134002

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Project description:BackgroundMeans to promote endogenous remyelination in multiple sclerosis (MS) benefit from insights into the role of inhibitory molecules that preclude remyelination. Fibronectin assembles into aggregates in MS, which impair oligodendrocyte differentiation and remyelination. Microglia and macrophages are required for complete remyelination and normally switch from a pro-inflammatory classical phenotype upon demyelination to a supportive alternative phenotype during remyelination. Here, we investigated the role of fibronectin aggregates in modulating microglia and macrophage behavior and phenotypes.MethodsBone marrow-derived macrophages and microglia from newborn rats were exposed to (a) plasma fibronectin coatings; (b) coatings of deoxycholate-insoluble fibronectin aggregates; (c) interferon-? (IFN?) treatment, as an inducer of the pro-inflammatory classically activated phenotype; (d) interleukin-4 (IL-4) treatment, to promote the pro-regenerative anti-inflammatory alternatively activated phenotype; or (e) left unstimulated on uncoated plastic. To examine the in vitro effects of the different stimulations on cell behavior and phenotype, proliferation, phagocytosis, morphology, and pro- and anti-inflammatory features were assessed.ResultsIn line with a classically activated phenotype, exposure of microglia and macrophages to both plasma fibronectin and fibronectin aggregates induced an amoeboid morphology and stimulated phagocytosis by macrophages. Furthermore, as observed upon IFN? treatment, coatings of aggregated, but not plasma fibronectin, promoted nitric oxide release by microglia and macrophages. Remarkably, fibronectin aggregates induced nitric oxide release in an integrin-independent manner. In addition, fibronectin aggregates, but not plasma fibronectin, increased the expression of arginase-1, similarly as observed upon treatment with IL-4. Proteomic analysis revealed that aggregates of fibronectin act as a scaffold for other proteins, including Hsp70 and thrombospondin-1, which may clarify the induction of both pro-inflammatory and anti-inflammatory features in macrophages cultured on fibronectin aggregate, but not plasma fibronectin coatings.ConclusionsMacrophages and microglia grown on aggregated fibronectin coatings adopt a distinct phenotype compared to plasma fibronectin coatings, showing pro-inflammatory and anti-inflammatory features. Therefore, the pathological fibronectin aggregates in MS lesions may impair remyelination by promoting and/or retaining several classically activated phenotypic features in microglia and macrophages.

Dataset Information

Alternatively Activated Macrophages Are Host Cells for Chlamydia trachomatis and Reverse Anti-chlamydial Classically Activated Macrophages.

Publications

Alternatively Activated Macrophages Are Host Cells for <i>Chlamydia trachomatis</i> and Reverse Anti-chlamydial Classically Activated Macrophages.

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