TLR2 and TLR4 triggering exerts contrasting effects with regard to HIV-1 infection of human dendritic cells and subsequent virus transfer to CD4+T cells

Thibault, Sandra; Fromentin, Rémi; Tardif, Maurice; Tremblay, Michel J.

doi:10.1186/1742-4690-6-42

Cited by 43 publications

(59 citation statements)

References 94 publications

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“…This indicates that NR signaling, in addition to directly repressing virus expression in infected cells, is capable of dampening the proinflammatory cytokine response that activates HIV-1 expression in an autocrine or paracrine fashion. , it is not surprising that a number of TLR ligands activate HIV-1 expression in immune cells (3,11,34,36,114,145,161). In agreement with other reports (3,11,36,98,114,145,161), we show that signaling through TLR2 activates HIV-1 expression in macrophages and DCs ( Fig.…”

Section: Nr Ligands Inhibit Hiv-1 Replication In Primary Macrophagessupporting

confidence: 81%

“…Second, STIs cause inflammation that leads to the recruitment of immune cells to the site of inflammation, thereby increasing the size of the HIV-1 target cell population (88,128,136). Third, STIs promote a favorable local environment for HIV-1 replication both by directly activating HIV-1 target cells and by inducing the release of cytokines that favor virus replication through the engagement of Toll-like receptors (TLRs) and other innate immune sensors in cells present in the mucosa (9,10,37,57,75,122,134,145,146,161).…”

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confidence: 99%

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Nuclear Receptor Signaling Inhibits HIV-1 Replication in Macrophages through Multipletrans-Repression Mechanisms

Hanley

Viglianti

2011

J Virol

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Section: Nr Ligands Inhibit Hiv-1 Replication In Primary Macrophagessupporting

confidence: 81%

mentioning

confidence: 99%

Nuclear Receptor Signaling Inhibits HIV-1 Replication in Macrophages through Multipletrans-Repression Mechanisms

Hanley

Viglianti

2011

J Virol

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“…24 Additionally, it has also been reported that coculture of DCs and CD4 + T cells increases HIV-1 transmission through TLR2 stimulation. 25 In HIV-1-infected patients, several alterations of TLR expression have been documented 23,[26][27][28][29] raising the possibility that during chronic infection proinflammatory signals can further augment HIV-1 genome expression. The expression and functions of TLRs have been extensively studied in cells from HIV-1-infected patients.…”

Section: Introductionmentioning

confidence: 99%

HIV Type 1 Infection Up-Regulates TLR2 and TLR4 Expression and Function in Vivo and in Vitro

Hernández

Stevenson

Latz

et al. 2012

AIDS Research and Human Retroviruses

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Toll-like receptors (TLRs) play a critical role in innate immunity against pathogens. Their stimulation induces the activation of NF-jB, an important inducer of HIV-1 replication. In recent years, an increasing number of studies using several cells types from HIV-infected patients indicate that TLRs play a key role in regulating the expression of proinflammatory cytokines and viral pathogenesis. In the present study, the effect of HIV-1 stimulation of monocyte-derived macrophage (MDM) and peripheral blood mononuclear cell (PBMC) subpopulations from healthy donors on the expression and functions of TLR2 and TLR4 was examined. In addition, and to complete the in vitro study, the expression pattern of TLR2 and TLR4 in 49 HIV-1-infected patients, classified according to viral load and the use of HAART, was determined and compared with 25 healthy subjects. An increase of TLR expression and production of proinflammatory cytokines were observed in MDMs and PBMCs infected with HIV-1 in vitro and in response to TLR stimulation, compared to the mock. In addition, an association between TLR expression and up-regulation of CD80 in plasmacytoid dendritic cells (pDCs) was observed. The ex vivo analysis indicated increased expression of TLR2 and TLR4 in myeloid dendritic cells (mDCs), but only of TLR2 in monocytes obtained from HIV-1-infected patients, compared to healthy subjects. Remarkably, the expression was higher in cells from patients who do not use HAART. In monocytes, there was a positive correlation between both TLRs and viral load, but not CD4 + T cell numbers. Together, our in vitro and ex vivo results suggest that TLR expression and function can be up-regulated in response to HIV-1 infection and could affect the inflammatory response. We propose that modulation of TLRs represents a mechanism to promote HIV-1 replication or AIDS progression in HIV-1-infected patients.

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“…The best-characterized class of these receptors is the family of Toll-like receptors (TLRs) that, upon recognition of conserved microbial-associated molecular patterns (MAMPs), trigger a cascade of signaling events that modulate both the adaptive and innate immune responses (19). TLR activation modulates HIV-1 infection and/or transmission, and, depending on the specific TLR agonist and the target cell, TLR activation can either promote or inhibit HIV-1 expression in vitro (17,18,(20)(21)(22)(23)(24)(25)(26).…”

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confidence: 99%

Neisseria gonorrhoeae-derived heptose elicits an innate immune response and drives HIV-1 expression

Malott¹,

Keller

Gaudet³

et al. 2013

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

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Clinical and epidemiological synergy exists between the globally important sexually transmitted infections, gonorrhea and HIV. Neisseria gonorrhoeae , which causes gonorrhea, is particularly adept at driving HIV-1 expression, but the molecular determinants of this relationship remain undefined. N. gonorrhoeae liberates a soluble factor that potently induces expression from the HIV-1 LTR in coinfected cluster of differentiation 4-positive (CD4 + ) T lymphocytes, but this factor is not a previously described innate effector. A genome-wide mutagenesis approach was undertaken to reveal which component(s) of N. gonorrhoeae induce HIV-1 expression in CD4 + T lymphocytes. A mutation in the ADP-heptose biosynthesis gene, hldA , rendered the bacteria unable to induce HIV-1 expression. The hldA mutant has a truncated lipooligosaccharide structure, contains lipid A in its outer membrane, and remains bioactive in a TLR4 reporter-based assay but did not induce HIV-1 expression. Mass spectrometry analysis of extensively fractionated N. gonorrhoeae- derived supernatants revealed that the LTR-inducing fraction contained a compound having a mass consistent with heptose-monophosphate (HMP). Heptose is a carbohydrate common in microbes but is absent from the mammalian glycome. Although ADP-heptose biosynthesis is common among Gram-negative bacteria, and heptose is a core component of most lipopolysaccharides, N. gonorrhoeae is peculiar in that it effectively liberates HMP during growth. This N. gonorrhoeae- derived HMP activates CD4 + T cells to invoke an NF-κB–dependent transcriptional response that drives HIV-1 expression and viral production. Our study thereby shows that heptose is a microbial-specific product that is sensed as an innate immune agonist and unveils the molecular link between N. gonorrhoeae and HIV-1.

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TLR2 and TLR4 triggering exerts contrasting effects with regard to HIV-1 infection of human dendritic cells and subsequent virus transfer to CD4+T cells

Cited by 43 publications

References 94 publications

Nuclear Receptor Signaling Inhibits HIV-1 Replication in Macrophages through Multipletrans-Repression Mechanisms

Nuclear Receptor Signaling Inhibits HIV-1 Replication in Macrophages through Multipletrans-Repression Mechanisms

HIV Type 1 Infection Up-Regulates TLR2 and TLR4 Expression and Function in Vivo and in Vitro

Neisseria gonorrhoeae-derived heptose elicits an innate immune response and drives HIV-1 expression

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