期刊
INFECTION AND IMMUNITY
卷 81, 期 1, 页码 2-10出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/IAI.00666-12
关键词
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资金
- NIH [T32-HL007118-33, R01 HL063655, R01 HL092811, K08AI064014]
- ALA biomedical research grant
Mycobacterium tuberculosis disease represents an enormous global health problem, with exceptionally high morbidity and mortality in HIV-seropositive (HIV+) persons. Alveolar macrophages from HIV+ persons demonstrate specific and targeted impairment of critical host cell responses, including impaired M. tuberculosis-mediated tumor necrosis factor (TNF) release and macrophage apoptosis. Vitamin D may promote anti-M. tuberculosis responses through upregulation of macrophage NO, NADPH oxidase, cathelicidin, and autophagy mechanisms, but whether vitamin D promotes anti-M. tuberculosis mechanisms in HIV+ macrophages is not known. In the current study, human macrophages exposed to M. tuberculosis demonstrated robust release of TNF, I kappa B degradation, and NF-kappa B nuclear translocation, and these responses were independent of vitamin D pretreatment. In marked contrast, HIV+ U1 human macrophages exposed to M. tuberculosis demonstrated very low TNF release and no significant I kappa B degradation or NF-kappa B nuclear translocation, whereas vitamin D pretreatment restored these critical responses. The vitamin D-mediated restored responses were dependent in part on macrophage CD14 expression. Importantly, similar response patterns were observed with clinically relevant human alveolar macrophages from healthy individuals and asymptomatic HIV+ persons at high clinical risk of M. tuberculosis infection. Taken together with the observation that local bronchoalveolar lavage fluid (BALF) levels of vitamin D are severely deficient in HIV+ persons, the data from this study demonstrate that exogenous vitamin D can selectively rescue impaired critical innate immune responses in vitro in alveolar macrophages from HIV+ persons at risk for M. tuberculosis disease, supporting a potential role for exogenous vitamin D as a therapeutic adjuvant in M. tuberculosis infection in HIV+ persons.
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