Impaired recognition of Mycobacterium tuberculosis by Alveolar Macrophages from diabetic mice

Martinez, Nuria, Ketheesan, Natkunam, West, Kim, Vallerskog, Therese, and Kornfeld, Hardy (2016) Impaired recognition of Mycobacterium tuberculosis by Alveolar Macrophages from diabetic mice. Journal of Infectious Diseases, 214 (11). pp. 1629-1637.

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Abstract

Background: Diabetes mellitus is associated with increased tuberculosis risk and severity. We previously reported that tuberculosis susceptibility in diabetic mice results from a delay in innate immune response to inhaled Mycobacterium tuberculosis, leading to delayed adaptive immune priming and, consequently, a higher plateau lung bacterial burden and greater immune pathology.

Methods: We tested the capacity of alveolar macrophages from diabetic mice to phagocytose M. tuberculosis ex vivo and promote T-cell activation in vivo.

Results: Alveolar macrophages from diabetic mice had reduced expression of CD14 and macrophage receptor with collagenous structure (MARCO), which recognize the bacterial cell wall component trehalose 6,6'-dimycolate (TDM). Diabetic alveolar macrophages exhibited reduced phagocytosis of M. tuberculosis or TDM-coated latex beads. This alveolar macrophage phenotype was absent in peritoneal and bone marrow-derived macrophages. Transfer of infected alveolar macrophages from diabetic mice into nondiabetic recipients confirmed an intrinsic alveolar macrophage defect that hindered T-cell priming. The diabetic alveolar macrophage phenotype depended in part on expression of the receptor for advanced glycation end products.

Conclusions: Reduced MARCO and CD14 expression contributes to defective sentinel function of alveolar macrophages, promoting tuberculosis susceptibility in diabetic hosts at a critical early step in the immune response to aerosol infection.

Item ID: 47632
Item Type: Article (Refereed Research - C1)
Keywords: Mycobacterium tuberculosis, diabetes, alveolar macrophages, phagocytosis, MARCO, CD14
ISSN: 1537-6613
Funders: National Institutes of Health (NIH)
Projects and Grants: NIH grant RO1 HL018849
Date Deposited: 08 Mar 2017 07:33
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1102 Cardiovascular Medicine and Haematology > 110203 Respiratory Diseases @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110702 Applied Immunology (incl Antibody Engineering, Xenotransplantation and T-cell Therapies) @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920104 Diabetes @ 50%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920115 Respiratory System and Diseases (incl. Asthma) @ 50%
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