Adiponectin Enhances Antibacterial Activity of Hematopoietic Cells by Suppressing Bone Marrow Inflammation

Yosuke Masamoto, Shunya Arai, Tomohiko Sato, Akihide Yoshimi, Naoto Kubota, Iseki Takamoto, Yoichiro Iwakura, Akihiko Yoshimura, Takashi Kadowaki, Mineo Kurokawa

Research output: Contribution to journalArticle

18 Citations (Scopus)

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. Infection is a well-known complication of obesity. Kurokawa and colleagues demonstrated that adiponectin deficiency in obese bone marrow leads to inflammatory cytokine milieu characterized by high TNF and inhibits emergency granulopoiesis upon systemic bacterial infection, highlighting adiponectin as a legitimate target for obesity-related bacterial infections.

Original languageEnglish
Pages (from-to)1422-1433
Number of pages12
JournalImmunity
Volume44
Issue number6
DOIs
Publication statusPublished - 2016 Jun 21

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Masamoto, Y., Arai, S., Sato, T., Yoshimi, A., Kubota, N., Takamoto, I., Iwakura, Y., Yoshimura, A., Kadowaki, T., & Kurokawa, M. (2016). Adiponectin Enhances Antibacterial Activity of Hematopoietic Cells by Suppressing Bone Marrow Inflammation. Immunity, 44(6), 1422-1433. https://doi.org/10.1016/j.immuni.2016.05.010