Type I Interferon Production Is Profoundly and Transiently Impaired in Primary HIV‐1 Infection

Kamga, Isabelle; Kahi, Sandrine; Develioglu, Leyla; Lichtner, Miriam; Marañón, Concepción; Deveau, Christiane; Meyer, Laurence; Goujard, Cécile; Lebon, Pierre; Sinet, Martine; Hosmalin, Anne

doi:10.1086/430931

Cited by 113 publications

(130 citation statements)

References 52 publications

Supporting

Mentioning

112

Contrasting

Unclassified

Order By: Relevance

“…pDC function may also be altered by HCV [35]. Infection with HIV also reduces pDC function, both in chronic and primary HIV infection although the decrease in function may be mostly due to reduced pDC numbers [36,37].…”

Section: Discussionmentioning

confidence: 99%

Dendritic cell activation and maturation induced by mucosal fluid from women with bacterial vaginosis

John

Martinson

Simões

et al. 2007

Clinical Immunology

View full text Add to dashboard Cite

Dendritic cells (DC) at mucosal surfaces mature when exposed to "danger" signals such as LPS. Bacterial vaginosis (BV) is a prevalent alteration of the vaginal bacterial flora associated with preterm childbirth and increased risk for HIV acquisition. We examined the effect of mucosal fluid from women with BV or healthy flora on DC function. IL-12, IL-23 and p40 production by monocytederived dendritic cells (MDDC) were all induced by BV samples. Activation/maturation markers HLA-DR, CD40, and CD83 on MDDC incubated with BV CVL were also induced. BV CVL also decreased the endocytic ability of MDDC and increased proliferation of T-cells in allogeneic MLR. Plasmacytoid dendritic cell (pDC) CD86 expression was induced by BV CVL. Healthy flora CVL had little effect in any of the tests. This study suggests that BV, but not healthy flora, affects local dendritic cell function in vivo suggesting a mechanism through which BV affects mucosal immunity.

show abstract

Section: Discussionmentioning

confidence: 99%

Dendritic cell activation and maturation induced by mucosal fluid from women with bacterial vaginosis

John

Martinson

Simões

et al. 2007

Clinical Immunology

View full text Add to dashboard Cite

show abstract

“…These effects can be partially reversed by antiretroviral therapy (14). Additionally, pDCs isolated from individuals acutely infected with HIV exhibit an impaired ability to secrete type 1 IFNs (15,16). The underlying cause(s) of these alterations in pDC numbers and activity, as a result of HIV infection, are unknown.…”

mentioning

confidence: 99%

HIV-1 gp120 inhibits TLR9-mediated activation and IFN-α secretion in plasmacytoid dendritic cells

Martinelli

Cicala²,

Ryk³

et al. 2007

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

185

172

View full text Add to dashboard Cite

Plasmacytoid dendritic cells (pDCs) play a central role in innate and adaptive immune responses against viral infections. pDCs secrete type I IFNs and proinflammatory cytokines upon stimulation by either TLR7 or TLR9. Throughout the course of HIV infection, the production of type-I IFNs is profoundly impaired, and total pDC cell counts in peripheral blood correlates inversely with viral load and positively with CD4 ؉ T cell count. The origin of these defects is unclear. pDCs express CD4, CCR5, and CXCR4, the primary receptor and coreceptors, respectively, for the HIV envelope; yet little is known concerning the effects of the viral envelope on these cells. Here, we show that exposure of pDCs to gp120 results in the suppression of activation of these cells. This suppression is specific for TLR9-mediated responses, because TLR7-mediated responses are unaffected by gp120. gp120 also suppressed TLR9-mediated induction of proinflammatory cytokines and expression of CD83, a marker of DC activation. Finally, gp120 suppressed pDC-induced cytolytic activity of natural killer cells. Taken together, these data demonstrate that the direct interaction of HIV-1 gp120 with pDCs interferes with TLR9 activation resulting in a decreased ability of pDCs to secrete antiviral and inflammatory factors that play a central role in initiating host immune responses against invading pathogens.CpG ͉ interferon ␣

show abstract

“…During retroviral infections, such as HIV, SIV, or Friend retro virus (FV), the type I IFN response is quite weak. It was shown that during primary HIV infection, type I IFNs are barely detectable because of a decrease of plasmacytoid DCs (26), the most important IFN-a producers. This was also observed in chronic HIV infections (27).…”

mentioning

confidence: 99%

Polyinosinic-Polycytidylic Acid Treatment of Friend Retrovirus-Infected Mice Improves Functional Properties of Virus-Specific T Cells and Prevents Virus-Induced Disease

Gibbert

Dietze

Zelinskyy

et al. 2010

The Journal of Immunology

View full text Add to dashboard Cite

The induction of type I IFN is the most immediate host response to viral infections. Type I IFN has a direct antiviral activity mediated by antiviral enzymes, but it also modulates the function of cells of the adaptive immune system. Many viruses can suppress type I IFN production, and in retroviral infections, the initial type I IFN is weak. Thus, one strategy of immunotherapy in viral infection is the exogenous induction of type I IFN during acute viral infection by TLR ligands. Along these lines, the TLR3/MDA5 ligand polyinosinic-polycytidylic acid [poly(I:C)] has already been used to treat viral infections. However, the immunological mechanisms underlying this successful therapy have not been defined until now. In this study, the Friend retrovirus (FV) mouse model was used to investigate the mode of action of poly(I:C) in antiretroviral immunotherapy. Postexposure, poly(I:C) treatment of FV-infected mice resulted in a significant reduction in viral loads and protection from virus-induced leukemia. This effect was IFN dependent because type I IFN receptor-deficient mice could not be protected by poly(I:C). The poly(I:C)-induced IFN response resulted in the expression of antiviral enzymes, which suppressed FV replication. Also, the virus-specific T cell response was augmented. Interestingly, it did not enhance the number of virus-specific CD4+ and CD8+ T cells, but rather the functional properties of these cells, such as cytokine production and cytotoxic activity. The results demonstrate a direct antiviral and immunomodulatory effect of poly(I:C) and, therefore, suggests its potential for clinical treatment of retroviral infections.

show abstract

Type I Interferon Production Is Profoundly and Transiently Impaired in Primary HIV‐1 Infection

Abstract: These data underline the potential for early antiretroviral treatment and IFN- alpha treatment to enhance viral control in a larger proportion of patients during the critical stage of primary infection.

Cited by 113 publications

References 52 publications

Dendritic cell activation and maturation induced by mucosal fluid from women with bacterial vaginosis

Dendritic cell activation and maturation induced by mucosal fluid from women with bacterial vaginosis

HIV-1 gp120 inhibits TLR9-mediated activation and IFN-α secretion in plasmacytoid dendritic cells

Polyinosinic-Polycytidylic Acid Treatment of Friend Retrovirus-Infected Mice Improves Functional Properties of Virus-Specific T Cells and Prevents Virus-Induced Disease

Contact Info

Product

Resources

About