Increased Escherichia coli-induced interleukin-23 production by CD16+ monocytes correlates with systemic immune activation in untreated HIV-1-infected individuals.
The level of microbial translocation from the intestine is increased in HIV-1 infection. Proinflammatory cytokine production by peripheral antigen-presenting cells in response to translocated microbes or microbial products may contribute to systemic immune activation, a hallmark of HIV-1 infection. We investigated the cytokine responses of peripheral blood myeloid dendritic cells (mDCs) and monocytes to in vitro stimulation with commensal enteric Escherichia coli in peripheral blood mononuclear cells (PBMC) from untreated HIV-1-infected subjects and from uninfected controls. Levels of interleukin 23 (IL-23) produced by PBMC from HIV-1-infected subjects in response to E. coli stimulation were significantly higher than those produced by PBMC from uninfected subjects. IL-23 was produced primarily by CD16(+) monocytes. This subset of monocytes was increased in frequency and expressed higher levels of Toll-like receptor 4 (TLR4) in HIV-1-infected individuals than in controls. Blocking TLR4 on total CD14(+) monocytes reduced IL-23 production in response to E. coli stimulation. Levels of soluble CD27, an indicator of systemic immune activation, were elevated in HIV-1-infected subjects and were associated with the percentage of CD16(+) monocytes and the induction of IL-23 by E. coli, providing a link between these parameters and systemic inflammation. Taken together, these results suggest that IL-23 produced by CD16(+) monocytes in response to microbial stimulation may contribute to systemic immune activation in HIV-1-infected individuals.
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Jennifer A
JA
Manuzak
Stephanie M
SM
Dillon
Eric J
EJ
Lee
Zachary M
ZM
Dong
Daniel K
DK
Hecht
Cara C
CC
Wilson
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology* / Q000502:physiology; D004927:Escherichia coli Infections / Q000209:etiology / Q000276:immunology* / Q000382:microbiology; D005260:Female; D058851:GPI-Linked Proteins / Q000276:immunology; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D016753:Interleukin-10; D053759:Interleukin-23 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology; D055815:Young Adult
C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D053759:Interleukin-23; D017452:Receptors, IgG; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D016753:Interleukin-10