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In contrast, simian immunodeficiency virus (SIV) infection of African-origin sooty mangabeys (SM) generally does not result in simian AIDS despite high viral loads and therefore affords a unique model in which to study the immunologic contributions to a nonpathogenic lentiviral disease outcome. A key feature of these natural SIV infections is the maintenance of low levels of immune activation during chronic infection. Our goal was to delineate the contribution of monocytes to maintaining low levels of immune activation in SIV-infected SM. Utilizing an<jats:italic>ex vivo<\/jats:italic>whole-blood assay, proinflammatory cytokine production was quantified in monocytes in response to multiple Toll-like receptor (TLR) ligands and a specific, significant reduction in the tumor necrosis factor alpha (TNF-\u03b1) response to lipopolysaccharide (LPS) was observed in SIV-infected SM. In contrast, monocytes from hosts of pathogenic infections (HIV-infected humans and SIV-infected Asian macaques) maintained a robust TNF-\u03b1 response. In SIV-infected SM, monocyte TNF-\u03b1 responses to low levels of LPS could be augmented by the presence of plasma from uninfected control animals. The impact of LPS-induced TNF-\u03b1 production on immune activation was demonstrated<jats:italic>in vitro<\/jats:italic>, as TNF-\u03b1 blocking antibodies inhibited downstream CD8<jats:sup>+<\/jats:sup>T cell activation in a dose-dependent manner. These data demonstrate an association between nonpathogenic SIV infection of SM and a reduced monocyte TNF-\u03b1 response to LPS, and they identify a role for monocytes in contributing to the suppressed chronic immune activation observed in these natural hosts.<\/jats:p>","DOI":"10.1128\/jvi.06813-11","type":"journal-article","created":{"date-parts":[[2012,5,3]],"date-time":"2012-05-03T01:53:16Z","timestamp":1336009996000},"page":"7605-7615","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":17,"title":["Simian Immunodeficiency Virus-Induced Alterations in Monocyte Production of Tumor Necrosis Factor Alpha Contribute to Reduced Immune Activation in Sooty Mangabeys"],"prefix":"10.1128","volume":"86","author":[{"given":"Kiran D.","family":"Mir","sequence":"first","affiliation":[{"name":"Seattle Biomedical Research Institute, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven E.","family":"Bosinger","sequence":"additional","affiliation":[{"name":"Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Gasper","sequence":"additional","affiliation":[{"name":"Seattle Biomedical Research Institute, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"On","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James G.","family":"Else","sequence":"additional","affiliation":[{"name":"Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA"},{"name":"Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason M.","family":"Brenchley","sequence":"additional","affiliation":[{"name":"National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Kelvin","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Silvestri","sequence":"additional","affiliation":[{"name":"Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA"},{"name":"Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiu-lok","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, University of Washington, Seattle, Washington, USA"},{"name":"Washington National Primate Research Center, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald L.","family":"Sodora","sequence":"additional","affiliation":[{"name":"Seattle Biomedical Research Institute, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.5.3099-3118.2003"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1970"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"6132","DOI":"10.4049\/jimmunol.154.11.6132","article-title":"HIV-1 infection of human macrophages impairs phagocytosis and killing of Toxoplasma gondii","volume":"154","author":"Biggs BA","year":"1995","unstructured":"BiggsBA HewishM KentS HayesK CroweSM. 1995. 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