RRC ID 48266
Author Masamoto Y, Arai S, Sato T, Yoshimi A, Kubota N, Takamoto I, Iwakura Y, Yoshimura A, Kadowaki T, Kurokawa M.
Title Adiponectin Enhances Antibacterial Activity of Hematopoietic Cells by Suppressing Bone Marrow Inflammation.
Journal Immunity
Abstract Obesity has been shown to increase the morbidity of infections, however, the underlying mechanisms remain largely unknown. Here we demonstrate that obesity caused adiponectin deficiency in the bone marrow (BM), which led to an inflamed BM characterized by increased tumor necrosis factor (TNF) production from bone marrow macrophages. Hematopoietic stem and progenitor cells (HSPCs) chronically exposed to excessive TNF in obese marrow aberrantly expressed cytokine signaling suppressor SOCS3, impairing JAK-STAT mediated signal transduction and cytokine-driven cell proliferation. Accordingly, both obese and adiponectin-deficient mice showed attenuated clearance of infected Listeria monocytogenes, indicating that obesity or loss of adiponectin is critical for exacerbation of infection. Adiponectin treatment restored the defective HSPC proliferation and bacterial clearance of obese and adiponectin-deficient mice, affirming the importance of adiponectin against infection. Taken together, our findings demonstrate that obesity impairs hematopoietic response against infections through a TNF-SOCS3-STAT3 axis, highlighting adiponectin as a legitimate target against obesity-related infections.
Volume 44(6)
Pages 1422-33
Published 2016-6-21
DOI 10.1016/j.immuni.2016.05.010
PII S1074-7613(16)30198-4
PMID 27317261
MeSH Adiponectin / genetics Adiponectin / metabolism* Animals Bacteriolysis Bone Marrow / immunology Cells, Cultured Diet Gene Expression Regulation Hematopoiesis Hematopoietic Stem Cell Mobilization Hematopoietic Stem Cells / physiology* Inflammation / immunology* Listeria monocytogenes / immunology* Listeriosis / immunology* Mice Mice, Inbred C57BL Mice, Knockout Obesity / immunology* Signal Transduction Suppressor of Cytokine Signaling 3 Protein / genetics Suppressor of Cytokine Signaling 3 Protein / metabolism Tumor Necrosis Factor-alpha / metabolism
IF 22.553
Times Cited 18
General Microbes JCM 7671