title: Macrophage accumulation in gut mucosa differentiates AIDS from chronic SIV infection in rhesus macaques.
abstract: The relationship between recruitment of mononuclear phagocytes to lymphoid and gut tissues and disease in HIV and SIV infection remains unclear. To address this question, we conducted cross-sectional analyses of dendritic cell (DC) subsets and CD163(+) macrophages in lymph nodes (LNs) and ileum of rhesus macaques with acute and chronic SIV infection and AIDS. In LNs significant differences were only evident when comparing uninfected and AIDS groups, with loss of myeloid DCs and CD103(+) DCs from peripheral and mesenteric LNs, respectively, and accumulation of plasmacytoid DCs and macrophages in mesenteric LNs. In contrast, there were fourfold more macrophages in ileum lamina propria in macaques with AIDS compared with chronic infection, and this increased to 40-fold in Peyer's patches. Gut macrophages exceeded plasmacytoid DCs and CD103(+) DCs by ten- to 17-fold in monkeys with AIDS but were at similar low frequencies as DCs in chronic infection. Gut macrophages in macaques with AIDS expressed IFN-α and TNF-α consistent with cell activation. CD163(+) macrophages also accumulated in gut mucosa in acute infection but lacked expression of IFN-α and TNF-α. These data reveal a relationship between inflammatory macrophage accumulation in gut mucosa and disease and suggest a role for macrophages in AIDS pathogenesis.
authors.affiliation: Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA, USA.|Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Zachary D
authors.initials: ZD
authors.lastname: Swan
authors.affiliation: Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA, USA.|Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Wonderlich
authors.affiliation: Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA, USA.|Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.|Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Simon M
authors.initials: SM
authors.lastname: Barratt-Boyes
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000208:Acute Disease; D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology*; D008253:Macaca mulatta; D008264:Macrophages / Q000276:immunology* / Q000821:virology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016898:Interferon-alpha; D014409:Tumor Necrosis Factor-alpha
keywords: AIDS; gut macrophages; lymphoid tissue; mononuclear phagocytes; nonhuman primate