Adiponectin Enhances Antibacterial Activity of Hematopoietic Cells by Suppressing Bone Marrow Inflammation.
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.
Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; Department of Transfusion Medicine, The University of Tokyo Hospital, Tokyo 113-8655, Japan.
Yosuke
Y
Masamoto
Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
Shunya
S
Arai
Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; Department of Transfusion Medicine, The University of Tokyo Hospital, Tokyo 113-8655, Japan.
Tomohiko
T
Sato
Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
Akihide
A
Yoshimi
Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
Naoto
N
Kubota
Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
Iseki
I
Takamoto
Division of Experimental Animal Immunology, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba 278-0022, Japan.
Yoichiro
Y
Iwakura
Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan.
Akihiko
A
Yoshimura
Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
Takashi
T
Kadowaki
Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan. Electronic address: kurokawa-tky@umin.ac.jp.
Mineo
M
Kurokawa
D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001433:Bacteriolysis; D001853:Bone Marrow / Q000276:immunology; D002478:Cells, Cultured; D004032:Diet; D005786:Gene Expression Regulation; D006410:Hematopoiesis; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D007249:Inflammation / Q000276:immunology*; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000276:immunology*; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D052242:Adiponectin; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D014409:Tumor Necrosis Factor-alpha