M2 Polarization of Human Macrophages Favors Survival of the Intracellular Pathogen Chlamydia pneumoniae

Buchacher, Tanja; Ohradanova‐Repic, Anna; Stockinger, Hannes; Fischer, Michael B.; Weber, Viktoria

doi:10.1371/journal.pone.0143593

Cited by 100 publications

(108 citation statements)

References 43 publications

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“…This was consistent with previous studies on iPSDM with another cell lineage which concluded that iPSDMs are fully mature but can be differentiated into M2 or M1 polarized cells13. Thus these cells were considered M0 macrophages that, like M2 macrophages but not M1 macrophages, are permissive for Chlamydia growth78.…”

Section: Resultssupporting

confidence: 90%

Exploiting induced pluripotent stem cell-derived macrophages to unravel host factors influencing Chlamydia trachomatis pathogenesis

et al. 2017

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Chlamydia trachomatis remains a leading cause of bacterial sexually transmitted infections and preventable blindness worldwide. There are, however, limited in vitro models to study the role of host genetics in the response of macrophages to this obligate human pathogen. Here, we describe an approach using macrophages derived from human induced pluripotent stem cells (iPSdMs) to study macrophage–Chlamydia interactions in vitro. We show that iPSdMs support the full infectious life cycle of C. trachomatis in a manner that mimics the infection of human blood-derived macrophages. Transcriptomic and proteomic profiling of the macrophage response to chlamydial infection highlighted the role of the type I interferon and interleukin 10-mediated responses. Using CRISPR/Cas9 technology, we generated biallelic knockout mutations in host genes encoding IRF5 and IL-10RA in iPSCs, and confirmed their roles in limiting chlamydial infection in macrophages. This model can potentially be extended to other pathogens and tissue systems to advance our understanding of host-pathogen interactions and the role of human genetics in influencing the outcome of infections.

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Section: Resultssupporting

confidence: 90%

Exploiting induced pluripotent stem cell-derived macrophages to unravel host factors influencing Chlamydia trachomatis pathogenesis

et al. 2017

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“…29 In vitro , these two phenotypes can be polarizable with the addition of IFN-γ/LPS or IL-4/IL-10. 30 …”

Section: Discussionmentioning

confidence: 99%

TSG-6 is highly expressed in human abdominal aortic aneurysms

Wang

Xie

Green

et al. 2017

Journal of Surgical Research

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Background The formation of abdominal aortic aneurysms (AAA) is characterized by a dominance of pro-inflammatory forces that result in smooth muscle cell apoptosis, extra-cellular matrix degradation, and progressive diameter expansion. Additional defects in the anti-inflammatory response may also play a role, but have yet to be fully characterized. TSG-6 (TNF-stimulated gene-6) is a potent anti-inflammatory protein involved in extracellular matrix stabilization and cell migration active in many pathological conditions. Here, we describe its role in AAA formation. Methods Blood and/or aortic tissue samples were collected from organ donors, subjects undergoing elective AAA screening, and open surgical AAA repair. Aortic specimens collected were preserved for IHC or immediately assayed after tissue homogenization. Protein concentrations in tissue and plasma were assayed by ELISA. All immune cell populations were assayed using FACS. In vitro, macrophage polarization from monocytes were performed with young, healthy donor PBMCs. Results TSG-6 was found to be abnormally elevated in both the plasma and aortic wall of patients with AAA compared to healthy and risk-factor matched non-AAA donors. We observed the highest tissue concentration of TSG-6 in the less diseased proximal and distal shoulders compared to the central aspect of the aneurysm. IHC localized most TSG-6 to the tunica media with minor expression in the tunica adventitia of the aortic wall. Higher concentrations of both M1 and M2 macrophages where also observed, however M1/M2 ratios were unchanged from healthy controls. We observed no difference in M1/M2 ratios in the peripheral blood of risk-factor matched non-AAA and AAA patients. Interesting, TSG-6 inhibited the polarization of the anti-inflammatory M2 phenotype in vitro. Conclusions AAA formation results from an imbalance of inflammatory forces causing aortic wall infiltration of mononuclear cells leading to vessel breakdown. In the AAA condition, we report an elevation of TSG-6 expression in both the aortic wall and the peripheral circulation.

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“…Indeed, M2 polarization of human macrophages was recently shown to favor also replication of Chlamydia pneumoniae (Buchacher et al, 2015). …”

Section: Metabolic Adaptations Of Iis Cells and The Ibpsmentioning

confidence: 99%

To Eat and to Be Eaten: Mutual Metabolic Adaptations of Immune Cells and Intracellular Bacterial Pathogens upon Infection

Eisenreich

Rudel

Heesemann

et al. 2017

Front. Cell. Infect. Microbiol.

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Intracellular bacterial pathogens (IBPs) invade and replicate in different cell types including immune cells, in particular of the innate immune system (IIS) during infection in the acute phase. However, immune cells primarily function as essential players in the highly effective and integrated host defense systems comprising the IIS and the adaptive immune system (AIS), which cooperatively protect the host against invading microbes including IBPs. As countermeasures, the bacterial pathogens (and in particular the IBPs) have developed strategies to evade or reprogram the IIS at various steps. The intracellular replication capacity and the anti-immune defense responses of the IBP's as well as the specific antimicrobial responses of the immune cells of the innate and the AIS depend on specific metabolic programs of the IBPs and their host cells. The metabolic programs of the immune cells supporting or counteracting replication of the IBPs appear to be mutually exclusive. Indeed, recent studies show that upon interaction of naïve, metabolically quiescent immune cells with IBPs, different metabolic activation processes occur which may result in the provision of a survival and replication niche for the pathogen or its eradication. It is therefore likely that within a possible host cell population subsets exist that are metabolically programmed for pro- or anti-microbial conditions. These metabolic programs may be triggered by the interactions between different bacterial agonistic components and host cell receptors. In this review, we summarize the current status in the field and discuss metabolic adaptation processes within immune cells of the IIS and the IBPs that support or restrict the intracellular replication of the pathogens.

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M2 Polarization of Human Macrophages Favors Survival of the Intracellular Pathogen Chlamydia pneumoniae

Cited by 100 publications

References 43 publications

Exploiting induced pluripotent stem cell-derived macrophages to unravel host factors influencing Chlamydia trachomatis pathogenesis

Exploiting induced pluripotent stem cell-derived macrophages to unravel host factors influencing Chlamydia trachomatis pathogenesis

TSG-6 is highly expressed in human abdominal aortic aneurysms

To Eat and to Be Eaten: Mutual Metabolic Adaptations of Immune Cells and Intracellular Bacterial Pathogens upon Infection

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