Channeling macrophage polarization by rocaglates increases macrophage resistance to Mycobacterium tuberculosis .

Autor:	Chatterjee S; Pulmonary Center, Department of Medicine, Boston University School of Medicine, National Emerging Infectious Diseases Laboratories (NEIDL), Boston University, Boston, MA 02118, USA., Yabaji SM; Pulmonary Center, Department of Medicine, Boston University School of Medicine, National Emerging Infectious Diseases Laboratories (NEIDL), Boston University, Boston, MA 02118, USA., Rukhlenko OS; Systems Biology Ireland, School of Medicine, University College Dublin, Dublin 4, Ireland., Bhattacharya B; Pulmonary Center, Department of Medicine, Boston University School of Medicine, National Emerging Infectious Diseases Laboratories (NEIDL), Boston University, Boston, MA 02118, USA., Waligurski E; Pulmonary Center, Department of Medicine, Boston University School of Medicine, National Emerging Infectious Diseases Laboratories (NEIDL), Boston University, Boston, MA 02118, USA., Vallavoju N; Department of Chemistry, Center for Molecular Discovery (BU-CMD), Boston University, Boston, MA 02215, USA., Ray S; Barnett Institute of Chemical and Biological Analysis, Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA., Kholodenko BN; Systems Biology Ireland, School of Medicine, University College Dublin, Dublin 4, Ireland.; Department of Pharmacology, Yale University School of Medicine, New Haven, USA., Brown LE; Department of Chemistry, Center for Molecular Discovery (BU-CMD), Boston University, Boston, MA 02215, USA., Beeler AB; Department of Chemistry, Center for Molecular Discovery (BU-CMD), Boston University, Boston, MA 02215, USA., Ivanov AR; Barnett Institute of Chemical and Biological Analysis, Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA., Kobzik L; Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA., Porco JA Jr; Department of Chemistry, Center for Molecular Discovery (BU-CMD), Boston University, Boston, MA 02215, USA., Kramnik I; Pulmonary Center, Department of Medicine, Boston University School of Medicine, National Emerging Infectious Diseases Laboratories (NEIDL), Boston University, Boston, MA 02118, USA.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2021 Jul 10; Vol. 24 (8), pp. 102845. Date of Electronic Publication: 2021 Jul 10 (Print Publication: 2021).
DOI:	10.1016/j.isci.2021.102845
Abstrakt:	Macrophages contribute to host immunity and tissue homeostasis via alternative activation programs. M1-like macrophages control intracellular bacterial pathogens and tumor progression. In contrast, M2-like macrophages shape reparative microenvironments that can be conducive for pathogen survival or tumor growth. An imbalance of these macrophages phenotypes may perpetuate sites of chronic unresolved inflammation, such as infectious granulomas and solid tumors. We have found that plant-derived and synthetic rocaglates sensitize macrophages to low concentrations of the M1-inducing cytokine IFN-gamma and inhibit their responsiveness to IL-4, a prototypical activator of the M2-like phenotype. Treatment of primary macrophages with rocaglates enhanced phagosome-lysosome fusion and control of intracellular mycobacteria. Thus, rocaglates represent a novel class of immunomodulators that can direct macrophage polarization toward the M1-like phenotype in complex microenvironments associated with hypofunction of type 1 and/or hyperactivation of type 2 immunity, e.g., chronic bacterial infections, allergies, and, possibly, certain tumors. Competing Interests: The authors declare no competing interests. (© 2021 The Authors.)
Databáze:	MEDLINE
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