Impaired Recognition of Mycobacterium tuberculosis by Alveolar Macrophages From Diabetic Mice.
J Infect Dis
; 214(11): 1629-1637, 2016 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-27630197
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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Fagocitose
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Ativação Linfocitária
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Macrófagos Alveolares
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Diabetes Mellitus
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Mycobacterium tuberculosis
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article