Cytomegalovirus blocks intestinal stroma-induced down-regulation of macrophage HIV-1 infection

Journal of Leukocyte Biology

Ronald Clements²  William J. Britt⁴  Devin Eckhoff²  Audrey J. Lazenby¹  Phillip D. Smith⁵  Akhil Maheshwari⁴  Lesley E. Smythies³  Xiaoyun Wu³  Lea Novak¹ 

[1] Pathology, and Pathology, and Pathology, and;Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA; and the Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA; and the Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA; and the;Medicine, Medicine, Medicine,;Departments of Pediatrics, Departments of Pediatrics, Departments of Pediatrics,;Medicine, VA Medical Center, Birmingham, Alabama, USA Medicine, Medicine, VA Medical Center, Birmingham, Alabama, USA VA Medical Center, Birmingham, Alabama, USA Medicine, VA Medical Center, Birmingham, Alabama, USA

关键词: mucosa;    intestinal macrophage;    extracellular matrix;    TNF-α;   

DOI  :  10.1189/jlb.0306230

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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 stroma-conditioned 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-α, but preinfection of the cells with CMV reversed this down-regulation, enhancing HIV-1 infection, p24 production, and TNF-α release. The ability of CMV to reverse S-CM down-regulation of macrophage HIV-1 infection was blocked by anti-TNF-α antibodies and over-ridden by exogenous TNF-α. Immunohistochemical analysis of monocyte-derived macrophages exposed to CMV and HIV-1 (YU2 pseudotype) 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-α proteins, others contained HIV-1 and TNF-α 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-α acting in trans to enhance HIV-1 infection.

【 授权许可】

Unknown