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Inhibitors of Apoptosis Protein Antagonists (Smac Mimetic Compounds) Control Polarization of Macrophages during Microbial Challenge and Sterile Inflammatory Responses

Please always quote using this URN: urn:nbn:de:bvb:20-opus-197484
  • Apoptosis is a physiological cell death process essential for development, tissue homeostasis, and for immune defense of multicellular animals. Inhibitors of apoptosis proteins (IAPs) regulate apoptosis in response to various cellular assaults. Using both genetic and pharmacological approaches we demonstrate here that the IAPs not only support opportunistic survival of intracellular human pathogens like Chlamydia pneumoniae but also control plasticity of iNOS+ M1 macrophage during the course of infection and render them refractory for immuneApoptosis is a physiological cell death process essential for development, tissue homeostasis, and for immune defense of multicellular animals. Inhibitors of apoptosis proteins (IAPs) regulate apoptosis in response to various cellular assaults. Using both genetic and pharmacological approaches we demonstrate here that the IAPs not only support opportunistic survival of intracellular human pathogens like Chlamydia pneumoniae but also control plasticity of iNOS+ M1 macrophage during the course of infection and render them refractory for immune stimulation. Treatment of Th1 primed macrophages with birinapant (IAP-specific antagonist) inhibited NO generation and relevant proteins involved in innate immune signaling. Accordingly, birinapant promoted hypoxia, angiogenesis, and tumor-induced M2 polarization of iNOS+ M1 macrophages. Interestingly, birinapant-driven changes in immune signaling were accompanied with changes in the expression of various proteins involved in the metabolism, and thus revealing the new role of IAPs in immune metabolic reprogramming in committed macrophages. Taken together, our study reveals the significance of IAP targeting approaches (Smac mimetic compounds) for the management of infectious and inflammatory diseases relying on macrophage plasticity.show moreshow less

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Metadaten
Author: Vinod Nadella, Aparna Mohanty, Lalita Sharma, Sailu Yellaboina, Hans-Joachim Mollenkopf, Varadendra Balaji Mazumdar, Ramesh Palaparthi, Madhavi B. Mylavarapu, Radheshyam Maurya, Sreenivasulu Kurukuti, Thomas Rudel, Hridayesh Prakash
URN:urn:nbn:de:bvb:20-opus-197484
Document Type:Journal article
Faculties:Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften
Language:English
Parent Title (English):Frontiers in Immunology
ISSN:1664-3224
Year of Completion:2018
Volume:8
Issue:1792
Source:Frontiers in Immunology (2018) 8:1792. doi: 10.3389/fimmu.2017.01792
DOI:https://doi.org/10.3389/fimmu.2017.01792
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Tag:apoptosis; hypothalamus; infection; inflammation mediators; macrophages immunobiology; polarization
Release Date:2020/08/17
Date of first Publication:2018/01/09
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International