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Stromal down-regulation of macrophage CD4/CCR5 expression and NF-κB activation mediates HIV-1 non-permissiveness in intestinal macrophages.

التفاصيل البيبلوغرافية
العنوان: Stromal down-regulation of macrophage CD4/CCR5 expression and NF-κB activation mediates HIV-1 non-permissiveness in intestinal macrophages.
المؤلفون: Ruizhong Shen, Gang Meng, Christina Ochsenbauer, Paul R Clapham, Jayleen Grams, Lea Novak, John C Kappes, Lesley E Smythies, Phillip D Smith
المصدر: PLoS Pathogens, Vol 7, Iss 5, p e1002060 (2011)
بيانات النشر: Public Library of Science (PLoS), 2011.
سنة النشر: 2011
المجموعة: LCC:Immunologic diseases. Allergy
LCC:Biology (General)
مصطلحات موضوعية: Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
الوصف: Tissue macrophages are derived exclusively from blood monocytes, which as monocyte-derived macrophages support HIV-1 replication. However, among human tissue macrophages only intestinal macrophages are non-permissive to HIV-1, suggesting that the unique microenvironment in human intestinal mucosa renders lamina propria macrophages non-permissive to HIV-1. We investigated this hypothesis using blood monocytes and intestinal extracellular matrix (stroma)-conditioned media (S-CM) to model the exposure of newly recruited monocytes and resident macrophages to lamina propria stroma, where the cells take up residence in the intestinal mucosa. Exposure of monocytes to S-CM blocked up-regulation of CD4 and CCR5 expression during monocyte differentiation into macrophages and inhibited productive HIV-1 infection in differentiated macrophages. Importantly, exposure of monocyte-derived macrophages simultaneously to S-CM and HIV-1 also inhibited viral replication, and sorted CD4+ intestinal macrophages, a proportion of which expressed CCR5+, did not support HIV-1 replication, indicating that the non-permissiveness to HIV-1 was not due to reduced receptor expression alone. Consistent with this conclusion, S-CM also potently inhibited replication of HIV-1 pseudotyped with vesicular stomatitis virus glycoprotein, which provides CD4/CCR5-independent entry. Neutralization of TGF-β in S-CM and recombinant TGF-β studies showed that stromal TGF-β inhibited macrophage nuclear translocation of NF-κB and HIV-1 replication. Thus, the profound inability of intestinal macrophages to support productive HIV-1 infection is likely the consequence of microenvironmental down-regulation of macrophage HIV-1 receptor/coreceptor expression and NF-κB activation.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1553-7366
1553-7374
Relation: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21637819/?tool=EBI; https://doaj.org/toc/1553-7366; https://doaj.org/toc/1553-7374
DOI: 10.1371/journal.ppat.1002060
URL الوصول: https://doaj.org/article/985fc87343b64f33b7824c049e030358
رقم الأكسشن: edsdoj.985fc87343b64f33b7824c049e030358
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:15537366
15537374
DOI:10.1371/journal.ppat.1002060