Anti-mycobacterial function of macrophages is impaired in a diet induced model of type 2 diabetes

被引:19
作者
Alim, Md Abdul [1 ]
Sikder, Suchandan [1 ]
Bridson, Tahnee L. [1 ]
Rush, Catherine M. [1 ]
Govan, Brenda L. [1 ]
Ketheesan, Natkunam [1 ]
机构
[1] James Cook Univ, Australian Inst Trop Hlth & Med, Infect Dis & Immunopathogenesis Res Grp, Coll Publ Hlth Med & Vet Sci, Townsville, Qld 4811, Australia
关键词
Murine model; Macrophage; Tuberculosis; Type; 2; diabetes; Phagocytosis; NONTUBERCULOUS MYCOBACTERIAL INFECTIONS; NITRIC-OXIDE SYNTHASE; NECROSIS-FACTOR-ALPHA; TUBERCULOSIS INFECTION; GAMMA-INTERFERON; IMMUNE-RESPONSES; DOUBLE BURDEN; MURINE MODEL; LONG-TERM; MICE;
D O I
10.1016/j.tube.2016.12.002
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Type 2 diabetes (T2D) is one of the major risk factors for tuberculosis (TB). In this study, a diet induced murine model of T2D (DIMT2D) was developed and characterized in the context of metabolic, biochemical and histopathological features following diet intervention. Mycobacterial susceptibility was investigated using Mycobacterium fortuitum as a surrogate. Phagocytic capability of alveolar macrophages and resident peritoneal macrophages were determined by in vitro assays using mycolic acid coated beads and M. fortuitum. Results demonstrated that bacillary loads were significantly higher in liver, spleen, and lungs of diabetic mice compared to controls. Higher inflammatory lesions and impaired cytokine kinetics (TNF-alpha, MCP-1, IL-12, IFN-gamma) were also observed in diabetic mice. Macrophages isolated from diabetic mice had lower uptake of mycolic acid coated beads, reduced bacterial internalization and killing and altered cytokine responses (TNF-alpha, IL-6, MCP-1). This model will be useful to further investigate different facets of host-pathogen interactions in TB-T2D. (C) 2016 Elsevier Ltd. All rights reserved.
引用
收藏
页码:47 / 54
页数:8
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