title: Plasmacytoid dendritic cells are recruited to the colorectum and contribute to immune activation during pathogenic SIV infection in rhesus macaques.
abstract: In SIV/HIV infection, the gastrointestinal tissue dominates as an important site because of the impact of massive mucosal CD4 depletion and immune activation-induced tissue pathology. Unlike AIDS-susceptible rhesus macaques, natural hosts do not progress to AIDS and resolve immune activation earlier. Here, we examine the role of dendritic cells (DCs) in mediating immune activation and disease progression. We demonstrate that plasmacytoid DCs (pDCs) in the blood up-regulate β7-integrin and are rapidly recruited to the colorectum after a pathogenic SIV infection in rhesus macaques. These pDCs were capable of producing proinflammatory cytokines and primed a T cytotoxic 1 response in vitro. Consistent with the up-regulation of β7-integrin on pDCs, in vivo blockade of α4β7-integrin dampened pDC recruitment to the colorectum and resulted in reduced immune activation. The up-regulation of β7-integrin expression on pDCs in the blood also was observed in HIV-infected humans but not in chronically SIV-infected sooty mangabeys that show low levels of immune activation. Our results uncover a new mechanism by which pDCs influence immune activation in colorectal tissue after pathogenic immunodeficiency virus infections.
authors.affiliation: Emory Vaccine Center, Department of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
authors.forename: Suefen
authors.initials: S
authors.lastname: Kwa
authors.forename: Sunil
authors.initials: S
authors.lastname: Kannanganat
authors.forename: Pragati
authors.initials: P
authors.lastname: Nigam
authors.forename: Mariam
authors.initials: M
authors.lastname: Siddiqui
authors.forename: Ravi Dyavar
authors.initials: RD
authors.lastname: Shetty
authors.forename: Wendy
authors.initials: W
authors.lastname: Armstrong
authors.forename: Aftab
authors.initials: A
authors.lastname: Ansari
authors.forename: Steven E
authors.initials: SE
authors.lastname: Bosinger
authors.forename: Guido
authors.initials: G
authors.lastname: Silvestri
authors.forename: Rama Rao
authors.initials: RR
authors.lastname: Amara
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D003106:Colon / Q000276:immunology* / Q000821:virology; D004279:DNA, Viral / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006678:HIV / Q000235:genetics / Q000472:pathogenicity; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D016023:Integrins / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012007:Rectum / Q000276:immunology* / Q000821:virology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000472:pathogenicity*; D019562:Viral Load
chemical_list: D015415:Biomarkers; D004279:DNA, Viral; D016023:Integrins; C071777:integrin alpha4beta7