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

Akhil Maheshwari, Lesley E. Smythies, Xiaoyun Wu, Lea Novak, Ronald Clements, Devin Eckhoff, Audrey J. Lazenby, William J. Britt, Phillip D. Smith

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1111-1117
Number of pages7
JournalJournal of Leukocyte Biology
Volume80
Issue number5
DOIs
StatePublished - Nov 1 2006

Keywords

  • Extracellular matrix
  • Intestinal macrophage
  • Mucosa
  • TNF-α

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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    Maheshwari, A., Smythies, L. E., Wu, X., Novak, L., Clements, R., Eckhoff, D., Lazenby, A. J., Britt, W. J., & Smith, P. D. (2006). Cytomegalovirus blocks intestinal stroma-induced down-regulation of macrophage HIV-1 infection. Journal of Leukocyte Biology, 80(5), 1111-1117. https://doi.org/10.1189/jlb.0306230