HIV-activated human plasmacytoid DCs induce Tregs through an indoleamine 2,3-dioxygenase–dependent mechanism

Manches, Olivier; Munn, David H.; Fallahi, Anahita; Lifson, Jeffrey D.; Chaperot, Laurence; Plumas, Joël; Bhardwaj, Nina

doi:10.1172/jci34823

Cited by 212 publications

(213 citation statements)

References 49 publications

Supporting

Mentioning

202

Contrasting

Unclassified

Order By: Relevance

“…IDO induction on HIV stimulation in pDCs is dependent on the TLR-7-MyD88 pathway, as demonstrated previously by an siRNA knockdown of TLR-7 and MyD88 (7). These experiments were performed with HIV laboratory strains, however.…”

Section: Resultsmentioning

confidence: 81%

“…We recently demonstrated that HIV-1-activated pDCs induce Treg differentiation from naïve CD4 + T cells through a CD4-, endocytosis-and Toll-like receptor (TLR)-7-dependent pathway (7). Importantly, using the competitive inhibitor 1-methyl-tryptophan and siRNA knockdown, we determined that expression of the enzyme IDO by pDC is absolutely required for Treg generation.…”

mentioning

confidence: 97%

“…In this context, plasmacytoid dendritic cells (pDCs), the major type I IFN producers on viral infection, seem to play an important role in Treg generation. pDCs can promote the differentiation of Tregs through several mechanisms, including the expression of inducible T-cell costimulatory ligand or the tryptophanmetabolizing enzyme indoleamine 2,3 dioxygenase (IDO) (5)(6)(7)(8).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Activation of the noncanonical NF-κB pathway by HIV controls a dendritic cell immunoregulatory phenotype

Manches

Fernandez

Plumas

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

HIV modulates plasmacytoid dendritic cell (pDC) activation via Tolllike receptor 7, inducing type I IFN and inflammatory cytokines. Simultaneously, pDCs up-regulate the expression of indoleamine 2,3 dioxygenase (IDO), which is essential for the induction of regulatory T cells (Tregs), which function to down-modulate immune activation. Here we demonstrate the crucial importance of the noncanonical NF-κB pathway in the establishment of this immunoregulatory phenotype in pDCs. In response to HIV, the noncanonical NF-κB pathway directly induces IDO and involves the recruitment of TNF receptorassociated factor-3 to the Toll-like receptor/MyD88 complex, NF-κB-inducing kinase-dependent IκB kinase-α activation, and p52/RelB nuclear translocation. We also show that pDC-induced Tregs can inhibit conventional DC (cDC) maturation partially through cytotoxic T-lymphocyte antigen (CTLA)-4 engagement. Furthermore, CTLA-4 induces IDO in cDCs in a NF-κB-inducing kinase-dependent way. These CTLA-4-conditioned cDCs can in turn induce Treg differentiation in an IDO-dependent manner. Thus, the noncanonical NF-κB pathway is integral in controlling immunoregulatory phenotypes of both pDCs and cDCs.

show abstract

Section: Resultsmentioning

confidence: 81%

mentioning

confidence: 97%

mentioning

confidence: 99%

See 1 more Smart Citation

Activation of the noncanonical NF-κB pathway by HIV controls a dendritic cell immunoregulatory phenotype

Manches

Fernandez

Plumas

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Enhanced generation of nTreg cells from the thymus,269 increased iTreg induction in the periphery,270, 271 and enhanced CD4 + Treg cell survival272 have all been suggested to contribute to this increase. Furthermore, as HIV‐specific Tregs are induced during infection,273, 274 the increase in CD4 + Treg frequencies may be, in part, driven by antigenic stimulation.…”

Section: Regulatory Cell Populations and Their Relationship To Bnab Imentioning

confidence: 99%

Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies

Borrow

Moody

2017

Immunological Reviews

View full text Add to dashboard Cite

SummaryInduction of broadly neutralizing antibodies (bnAbs) capable of inhibiting infection with diverse variants of human immunodeficiency virus type 1 (HIV‐1) is a key, as‐yet‐unachieved goal of prophylactic HIV‐1 vaccine strategies. However, some HIV‐infected individuals develop bnAbs after approximately 2‐4 years of infection, enabling analysis of features of these antibodies and the immunological environment that enables their induction. Distinct subsets of CD4+ T cells play opposing roles in the regulation of humoral responses: T follicular helper (Tfh) cells support germinal center formation and provide help for affinity maturation and the development of memory B cells and plasma cells, while regulatory CD4+ (Treg) cells including T follicular regulatory (Tfr) cells inhibit the germinal center reaction to limit autoantibody production. BnAbs exhibit high somatic mutation frequencies, long third heavy‐chain complementarity determining regions, and/or autoreactivity, suggesting that bnAb generation is likely to be highly dependent on the activity of CD4+ Tfh cells, and may be constrained by host tolerance controls. This review discusses what is known about the immunological environment during HIV‐1 infection, in particular alterations in CD4+ Tfh, Treg, and Tfr populations and autoantibody generation, and how this is related to bnAb development, and considers the implications for HIV‐1 vaccine design.

show abstract

“…More recent data have shown that PDCs, especially when unstimulated or alternatively stimulated, or in certain anatomical locations, act as tolerogenic instead of immunogenic cells. This may occur via different mechanisms, such as secretion of granzyme B (GrB) to impair T-cell proliferation [30] or by production of indoleamine-2,3-dioxygenase (IDO) to promote regulatory T-cell generation [31,32].…”

Section: Background On Pdcs: History and Functionmentioning

confidence: 99%

Trafficking properties of plasmacytoid dendritic cells in health and disease

Sozzani

Vermi

Prete

et al. 2010

Trends in Immunology

146

151

View full text Add to dashboard Cite

HIV-activated human plasmacytoid DCs induce Tregs through an indoleamine 2,3-dioxygenase–dependent mechanism

Cited by 212 publications

References 49 publications

Activation of the noncanonical NF-κB pathway by HIV controls a dendritic cell immunoregulatory phenotype

Activation of the noncanonical NF-κB pathway by HIV controls a dendritic cell immunoregulatory phenotype

Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies

Trafficking properties of plasmacytoid dendritic cells in health and disease

Contact Info

Product

Resources

About