期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 80, 期 5, 页码 1111-1117出版社
WILEY
DOI: 10.1189/jlb.0306230
关键词
mucosa; intestinal macrophage; extracellular matrix; TNF-alpha
资金
- NICHD NIH HHS [HD-41361] Funding Source: Medline
- NIDCR NIH HHS [DE-16005] Funding Source: Medline
- NIDDK NIH HHS [DK-54495, DK-47322, DK-74033] Funding Source: Medline
Intestinal macrophages, unlike macrophages from other tissues, do not support HIV-1 infection or produce proinflammatory cytokines. In vitro studies suggest this unique, functional phenotype is a result of the exposure of newly recruited blood monocytes to intestinal stromal products. However, in AIDS-related CMV colitis, mucosal macrophages express HIV-1 and proinflammatory cytokines. Therefore, we investigated the mechanism by which CMV confers permissiveness to HIV-1 and cytokine production on intestinal macrophages. We show that intestinal stromaconditioned media (S-CM) down-regulated monocyte-derived macrophage infection by HIV-1 (pseudotyped with YU2 envelope or vesicular stomatitis virus glycoprotein) and production of TNF-alpha, but preinfection of the cells with CMV reversed this down-regulation, enhancing HIV-1 infection, p24 production, and TNF-alpha release. The ability of CMV to reverse S-CM down-regulation of macrophage HIV-1 infection was blocked by anti-TNF-alpha antibodies and over-ridden by exogenous TNF-alpha. Imunmohistochemical analysis of monocyte-derived macrophages exposed to CMV and HIV-1 (YU2 psendotype) revealed that the cells infrequently contained CMV and HIV-1 viral proteins. In addition, analysis of colon tissue sections from HIV-1-infected patients with CMV colitis showed that some macrophage-like cells contained CMV and TNF-alpha proteins, others contained HIV-1 and TNF-alpha proteins, but cells infrequently contained CMV and HIV-1 proteins. These results indicate that CMV blocks stromal product inhibition of HIV-1 infection in macrophages, and this inhibition is mediated, at least in part, by CMV-induced TNF-alpha acting in trans to enhance HIV-1 infection. J. Leukoc. Biol. 80: 1111-1117; 2006.
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