PMID- 25921339 OWN - NLM STAT- MEDLINE DCOM- 20160927 LR - 20231213 IS - 1935-3456 (Electronic) IS - 1933-0219 (Print) IS - 1933-0219 (Linking) VI - 9 IP - 1 DP - 2016 Jan TI - Gut dendritic cell activation links an altered colonic microbiome to mucosal and systemic T-cell activation in untreated HIV-1 infection. PG - 24-37 LID - 10.1038/mi.2015.33 [doi] AB - HIV-1-associated disruption of intestinal homeostasis is a major factor contributing to chronic immune activation and inflammation. Dendritic cells (DCs) are crucial in maintaining intestinal homeostasis, but the impact of HIV-1 infection on intestinal DC number and function has not been extensively studied. We compared the frequency and activation/maturation status of colonic myeloid DC (mDC) subsets (CD1c(+) and CD1c(neg)) and plasmacytoid DCs in untreated HIV-1-infected subjects with uninfected controls. Colonic mDCs in HIV-1-infected subjects had increased CD40 but decreased CD83 expression, and CD40 expression on CD1c(+) mDCs positively correlated with mucosal HIV-1 viral load, with mucosal and systemic cytokine production, and with frequencies of activated colon and blood T cells. Percentage of CD83(+)CD1c(+) mDCs negatively correlated with frequencies of interferon-gamma-producing colon CD4(+) and CD8(+) T cells. CD40 expression on CD1c(+) mDCs positively associated with abundance of high prevalence mucosal Prevotella copri and Prevotella stercorea but negatively associated with a number of low prevalence mucosal species, including Rumminococcus bromii. CD1c(+) mDC cytokine production was greater in response to in vitro stimulation with Prevotella species relative to R. bromii. These findings suggest that, during HIV infection, colonic mDCs become activated upon exposure to mucosal pathobiont bacteria leading to mucosal and systemic immune activation. FAU - Dillon, S M AU - Dillon SM AD - Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. FAU - Lee, E J AU - Lee EJ AD - Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. FAU - Kotter, C V AU - Kotter CV AD - Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. FAU - Austin, G L AU - Austin GL AD - Department of Gastroenterology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. FAU - Gianella, S AU - Gianella S AD - Division of Infectious Diseases, University of California San Diego, La Jolla, California, USA. FAU - Siewe, B AU - Siewe B AD - Department of Immunology-Microbiology, Rush University Medical Center, Chicago, Illinois, USA. FAU - Smith, D M AU - Smith DM AD - Division of Infectious Diseases, University of California San Diego, La Jolla, California, USA. FAU - Landay, A L AU - Landay AL AD - Department of Immunology-Microbiology, Rush University Medical Center, Chicago, Illinois, USA. FAU - McManus, M C AU - McManus MC AD - Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. FAU - Robertson, C E AU - Robertson CE AD - Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. AD - University of Colorado Microbiome Research Consortium, Aurora, Colorado, USA. FAU - Frank, D N AU - Frank DN AD - Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. AD - University of Colorado Microbiome Research Consortium, Aurora, Colorado, USA. FAU - McCarter, M D AU - McCarter MD AD - Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. FAU - Wilson, C C AU - Wilson CC AD - Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. LA - eng GR - R01 DK088663/DK/NIDDK NIH HHS/United States GR - R01 AI108404/AI/NIAID NIH HHS/United States GR - R24 AI106039/AI/NIAID NIH HHS/United States GR - AI36214/AI/NIAID NIH HHS/United States GR - UL1 TR000154/TR/NCATS NIH HHS/United States GR - P30 AI036214/AI/NIAID NIH HHS/United States GR - UL1 TR001082/TR/NCATS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20150429 PL - United States TA - Mucosal Immunol JT - Mucosal immunology JID - 101299742 RN - 0 (Antigens, CD) RN - 0 (Antigens, CD1) RN - 0 (CD1C protein, human) RN - 0 (CD40 Antigens) RN - 0 (Glycoproteins) RN - 0 (Immunoglobulins) RN - 0 (Membrane Glycoproteins) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Adult MH - Antigens, CD/genetics/immunology MH - Antigens, CD1/genetics/immunology MH - CD4-Positive T-Lymphocytes/*immunology/microbiology MH - CD40 Antigens/genetics/immunology MH - CD8-Positive T-Lymphocytes/*immunology/microbiology MH - Case-Control Studies MH - Cell Lineage/immunology MH - Colon/*immunology/microbiology MH - Dendritic Cells/immunology/microbiology MH - Female MH - Gastrointestinal Microbiome/*immunology MH - Gene Expression Regulation MH - Glycoproteins/genetics/immunology MH - HIV Infections/*immunology/microbiology/pathology MH - HIV-1/*immunology MH - Humans MH - Immunoglobulins/genetics/immunology MH - Interferon-gamma/genetics/immunology MH - Lymphocyte Activation MH - Male MH - Membrane Glycoproteins/genetics/immunology MH - Middle Aged MH - Mucous Membrane/*immunology/microbiology MH - Prevotella/growth & development/immunology MH - Ruminococcus/growth & development/immunology MH - Signal Transduction MH - Viral Load MH - CD83 Antigen PMC - PMC4626441 MID - NIHMS673899 COIS- DISCLOSURE The authors declare no conflict of interest. EDAT- 2015/04/30 06:00 MHDA- 2016/09/28 06:00 PMCR- 2016/05/18 CRDT- 2015/04/30 06:00 PHST- 2014/12/17 00:00 [received] PHST- 2015/03/03 00:00 [accepted] PHST- 2015/04/30 06:00 [entrez] PHST- 2015/04/30 06:00 [pubmed] PHST- 2016/09/28 06:00 [medline] PHST- 2016/05/18 00:00 [pmc-release] AID - S1933-0219(22)00840-6 [pii] AID - 10.1038/mi.2015.33 [doi] PST - ppublish SO - Mucosal Immunol. 2016 Jan;9(1):24-37. doi: 10.1038/mi.2015.33. Epub 2015 Apr 29.