Gut dendritic cell activation links an altered colonic microbiome to mucosal and systemic T-cell activation in untreated HIV-1 infection.
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-γ-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.
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
S M
SM
Dillon
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
E J
EJ
Lee
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
C V
CV
Kotter
Department of Gastroenterology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
G L
GL
Austin
Division of Infectious Diseases, University of California San Diego, La Jolla, California, USA.
S
S
Gianella
Department of Immunology-Microbiology, Rush University Medical Center, Chicago, Illinois, USA.
B
B
Siewe
Division of Infectious Diseases, University of California San Diego, La Jolla, California, USA.
D M
DM
Smith
Department of Immunology-Microbiology, Rush University Medical Center, Chicago, Illinois, USA.
A L
AL
Landay
Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
M C
MC
McManus
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.|University of Colorado Microbiome Research Consortium, Aurora, Colorado, USA.
C E
CE
Robertson
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.|University of Colorado Microbiome Research Consortium, Aurora, Colorado, USA.
D N
DN
Frank
Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
M D
MD
McCarter
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
C C
CC
Wilson
D000328:Adult; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D019013:CD40 Antigens / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D016022:Case-Control Studies; D019070:Cell Lineage / Q000276:immunology; D003106:Colon / Q000276:immunology* / Q000382:microbiology; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D008875:Middle Aged; D009092:Mucous Membrane / Q000276:immunology* / Q000382:microbiology; D018720:Prevotella / Q000254:growth & development / Q000276:immunology; D045857:Ruminococcus / Q000254:growth & development / Q000276:immunology; D015398:Signal Transduction; D019562:Viral Load; D000097802:CD83 Antigen
D015703:Antigens, CD; D018949:Antigens, CD1; D019013:CD40 Antigens; D006023:Glycoproteins; D007136:Immunoglobulins; D007371:Interferon-gamma; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen; C437944:CD1C protein, human