HIV-1 selectively targets gut-homing CCR6+CD4+ T cells via mTOR-dependent mechanisms

Planas, Delphine; Zhang, Yuwei; Monteiro, Patricia; Goulet, Jean-Philippe; Gosselin, Annie; Grandvaux, Nathalie; Hope, Thomas J.; Fassati, Ariberto; Routy, Jean Pierre; Ancuța, Petronela

doi:10.1172/jci.insight.93230

Cited by 79 publications

(182 citation statements)

References 95 publications

Supporting

Mentioning

164

Contrasting

Unclassified

Order By: Relevance

“…90 We demonstrated that RA acts on memory CD4 1 T-cells to increases HIV permissiveness in Th17 cells via mechanistic target of rapamycin-dependent mechanisms. 59,64 Thus, by producing RA, CD16 1 MDDCs may either act as regulatory DCs or activate Th17 cells to promote HIV dissemination at mucosal level. 13,91 Indeed, CD16 1 monocytes express high levels of CX3CR1, 30,31 a chemokine receptor mediating migration into the gut, 92 and they may differentiate into mucosal CD103 1 RALDH2 1 DCs.…”

Section: Discussionmentioning

confidence: 99%

“…HIV viral stocks were prepared by transfection of 293T cells with the appropriate plasmid; the concentration of HIV stocks was determined by ELISA quantification of HIV-p24 protein; and HIV infectivity was titrated on primary CD4 1 T cells, as previously described. [57][58][59][60] Total RNA was isolated using RNeasy columns kit (Qiagen). RNA quantity was determined by Pearl NanoPhotometer (Implen, Germany; 1-5 mg RNA/10 6 cells).…”

Section: Genome-wide Transcriptional Profilingmentioning

confidence: 99%

“…60,61 Differentially expressed genes were adjusted using Benjamini-Hochberg method for multiple hypotheses testing, as we previously reported. [57][58][59] This allowed the use of false discovery rate thresholds to assess whether a gene is differentially expressed or not. Differentially expressed genes were further identified (cutoff 1.3-fold; P , .05; adjusted [adj.]…”

Section: Genome-wide Transcriptional Profilingmentioning

confidence: 99%

“…56,57 Corresponding heat maps for biological function categories were generated using programming language R. 56 The clustering was performed using the complete linkage method on the Euclidean distances from the values represented in the heat maps, as we previously reported. [57][58][59] Although these methods are known to be "unsupervised," clustering samples with a subset of differentially expressed genes are considered as "supervised. "…”

Section: Genome-wide Transcriptional Profilingmentioning

confidence: 99%

See 3 more Smart Citations

CD16+ monocytes give rise to CD103+RALDH2+TCF4+ dendritic cells with unique transcriptional and immunological features

et al. 2018

Self Cite

View full text Add to dashboard Cite

Classical CD16− vs intermediate/nonclassical CD16+ monocytes differ in their homing potential and biological functions, but whether they differentiate into dendritic cells (DCs) with distinct contributions to immunity against bacterial/viral pathogens remains poorly investigated. Here, we employed a systems biology approach to identify clinically relevant differences between CD16+ and CD16− monocyte-derived DCs (MDDCs). Although both CD16+ and CD16− MDDCs acquire classical immature/mature DC markers in vitro, genome-wide transcriptional profiling revealed unique molecular signatures for CD16+ MDDCs, including adhesion molecules (ITGAE/CD103), transcription factors (TCF7L2/TCF4), and enzymes (ALDH1A2/RALDH2), whereas CD16− MDDCs exhibit a CDH1/E-cadherin+ phenotype. Of note, lipopolysaccharides (LPS) upregulated distinct transcripts in CD16+ (eg, CCL8, SIGLEC1, MIR4439, SCIN, interleukin [IL]-7R, PLTP, tumor necrosis factor [TNF]) and CD16− MDDCs (eg, MMP10, MMP1, TGM2, IL-1A, TNFRSF11A, lysosomal-associated membrane protein 1, MMP8). Also, unique sets of HIV-modulated genes were identified in the 2 subsets. Further gene set enrichment analysis identified canonical pathways that pointed to “inflammation” as the major feature of CD16+ MDDCs at immature stage and on LPS/HIV exposure. Finally, functional validations and meta-analysis comparing the transcriptome of monocyte and MDDC subsets revealed that CD16+ vs CD16− monocytes preserved their superior ability to produce TNF-α and CCL22, as well as other sets of transcripts (eg, TCF4), during differentiation into DC. These results provide evidence that monocyte subsets are transcriptionally imprinted/programmed with specific differentiation fates, with intermediate/nonclassical CD16+ monocytes being precursors for pro-inflammatory CD103+RALDH2+TCF4+ DCs that may play key roles in mucosal immunity homeostasis/pathogenesis. Thus, alterations in the CD16+/CD16− monocyte ratios during pathological conditions may dramatically influence the quality of MDDC-mediated immunity.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Genome-wide Transcriptional Profilingmentioning

confidence: 99%

Section: Genome-wide Transcriptional Profilingmentioning

confidence: 99%

Section: Genome-wide Transcriptional Profilingmentioning

confidence: 99%

See 2 more Smart Citations

CD16+ monocytes give rise to CD103+RALDH2+TCF4+ dendritic cells with unique transcriptional and immunological features

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…Th17 and Th22 cells are routinely observed to be preferentially depleted from mucosal sites of HIV-infected humans and SIV-infected Asian macaques (reviewed in references 17 and 43) and represent some of the first cells infected after intravaginal infection (19). Moreover, CCR6 ϩ CD4 T cells are exquisitely sensitive to infection in vitro, and naive CD4 T cells that are infected do not efficiently differentiate into Th17 cells (18,44,45). Thus, specific targeting of CCR6 ϩ CD4 T cells (including CD4 T cells capable of producing IL-17 and IL-22) by HIV/SIV might explain their preferential loss.…”

Section: Discussionmentioning

confidence: 99%

Simian Immunodeficiency Virus Infects Functionally Polarized Memory CD4 T Cells Equivalently In Vivo

Lai

Starke

Flynn

et al. 2019

J Virol

View full text Add to dashboard Cite

Among the numerous immunological abnormalities observed in chronically human immunodeficiency virus (HIV)-infected individuals, perturbations in memory CD4 T cells are thought to contribute specifically to disease pathogenesis. Among these, functional imbalances in the frequencies of T regulatory cells (Tregs) and interleukin 17 (IL-17)/IL-22-producing Th cells (Th17/Th22) from mucosal sites and T follicular helper (Tfh) cells in lymph nodes are thought to facilitate specific aspects of disease pathogenesis. However, while preferential infection of Tfh cells is widely thought to create an important viral reservoir in an immunologically privileged site in vivo, whether immunological perturbations among memory CD4 T cell populations are attributable to their relative infectivity by the virus in vivo is unclear.Here we studied peripheral blood and lymphoid tissues from antiretroviral (ARV)treated and ARV-naive Asian macaques and isolated functionally defined populations of memory CD4 T cells. We then assessed the degree to which these populations were infected by simian immunodeficiency virus (SIV) in vivo, to determine whether particular functionally identified populations of memory CD4 T cells were preferentially infected by the virus. We found that SIV did not preferentially infect Th17 cells, compared to Th1 cells, Th2 cells, or Tregs. Moreover, Th17 cells contributed proportionately to the total pool of infected cells. Taken together, our data suggest that, although Tfh cells are more prone to harbor viral DNA, other functionally polarized cells are equally infected by the virus in vivo and Th17 cells are not preferentially infected. IMPORTANCE Functional perturbations of memory CD4 T cells have been suggested to underlie important aspects of HIV disease progression. However, the mechanisms underlying these perturbations remain unclear. Using a nonhuman primate model of HIV, we show that SIV infects functionally defined populations of memory CD4 T cells equally in different anatomic sites. Thus, preferential infection by the virus is unlikely to cause functional perturbations.

show abstract

More than a Gender Issue: Testis as a Distinctive HIV Reservoir and Its Implication for Viral Eradication

Routy

Dupuy

Lin

et al. 2022

Methods in Molecular Biology

View full text Add to dashboard Cite

HIV-1 selectively targets gut-homing CCR6+CD4+ T cells via mTOR-dependent mechanisms

Cited by 79 publications

References 95 publications

CD16+ monocytes give rise to CD103+RALDH2+TCF4+ dendritic cells with unique transcriptional and immunological features

CD16+ monocytes give rise to CD103+RALDH2+TCF4+ dendritic cells with unique transcriptional and immunological features

Simian Immunodeficiency Virus Infects Functionally Polarized Memory CD4 T Cells Equivalently In Vivo

More than a Gender Issue: Testis as a Distinctive HIV Reservoir and Its Implication for Viral Eradication

Contact Info

Product

Resources

About