Toll-like receptor expression and responsiveness are increased in viraemic HIV-1 infection

Lester, Richard; Yao, Xiao‐Dan; Ball, T. Blake; McKinnon, Lyle R.; Kaul, Rupert; Wachihi, Charles; Jaoko, Walter; Plummer, Francis A.; Rosenthal, Kenneth L.

doi:10.1097/qad.0b013e3282f4de35

Cited by 133 publications

(153 citation statements)

References 63 publications

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“…Interestingly, in monocytes expression of TLR2 and TLR4 was positively correlated with viral load, as well as TLR2 in pDCs, all of them in patients without HAART. This is similar to previous reports in chronically HIV-1-infected patients with advanced disease (CD4 + T cell count less than 200 cells/ ml), 23,27 as well as in coinfected patients with HIV-1 and opportunistic infections. 34 Regarding other TLRs, previous studies have shown lower levels of TLR3, TLR7, and TLR9 in patients with high levels of HIV-1 RNA compared to those with lower levels of viremia.…”

supporting

confidence: 81%

“…Likewise, it has been reported that HIV-1 and its products can also modulate TLR expression and functions. 27,50 For instance, ssRNA40 (HIV-1-derived RNA) increases TLR3 and TLR8 expression in activated T cells, 39 as well as TLR4 mRNA expression, 23,27 resulting in an increase in proinflammatory cytokine production in response to TLR stimulation by HIV-1. Increased TLR4 expression by T cell subsets has been reported in HIV-1-infected patients 28 ; in chronic HIV-1-infected patients who failed to respond to HAART, reduced expression of TLR3, TLR4, and TLR9 together with increased expression of TLR7, which correlated with high HIV-1 RNA levels, was reported.…”

Section: Discussionmentioning

confidence: 99%

“…34 All of these studies were obtained using cells derived from HIV-1-infected patients that have shown increased response in the presence of TLR ligands. 23 Here, using MDMs or PBMCs from healthy subjects and infected in vitro with HIV-1 and stimulated with specific FIG. 8.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, in peripheral blood mononuclear cells (PBMCs) derived from chronic untreated HIV-1-infected patients, an increase in TLR6, TLR7, and TLR8 mRNA was reported; in contrast, in HIV-1-infected patients with advanced disease, an mRNA increase was observed for TLR2, TLR3, and TLR4. 23 Using PBMCs from HIV-1-infected patients, also reported the up-regulation of several chemokines through TLR2 stimulation, compared to PBMCs derived from healthy donors. 24 Additionally, it has also been reported that coculture of DCs and CD4 + T cells increases HIV-1 transmission through TLR2 stimulation.…”

Section: Introductionmentioning

confidence: 99%

“…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%

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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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supporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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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Susceptibility to HIV‐1 infection is influenced by toll like receptor‐2 (−196 to −174) polymorphism in a north Indian population

Vidyant

Chatterjee

Agarwal

et al. 2017

The Journal of Gene Medicine

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Prophylactic and therapeutic implications of toll‐like receptor ligands

Hedayat

Takeda

Rezaei

2010

Medicinal Research Reviews

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The evolutionary conserved Toll-like receptors (TLRs) are the first identified and best characterized pattern recognition receptors (PRRs) which discriminate self from nonself, providing an early and effective immune response against invading pathogens. The ever expanding knowledge of TLR signaling network make it one of the most promising therapeutic strategies to modulate the immune response in various human diseases. Immune modulating strategies based on TLR-specific agonists elicit a potent immune response to adjuvant vaccine immunotherapy, cancers, allergic diseases, and chronic viral infections while minimizing the risk of uncontrolled provocation of systemic inflammatory response. Moreover, the contribution of TLR signaling in the pathogenesis of chronic noninfectious inflammatory and autoimmune diseases provides the rationale for the development and clinical implementation of TLR-specific antagonists. At present, a few TLR-specific agonists have been approved for both prophylactic and therapeutic applications, while the ongoing preclinical and clinical studies show promising results on various novel therapeutic molecules as an adjunctive to conventional pharmacotherapy or stand-alone therapeutic strategy.

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Toll-like receptor expression and responsiveness are increased in viraemic HIV-1 infection

Abstract: Together, these data indicate that chronic viraemic HIV-1 is associated with increased TLR expression and responsiveness, which may perpetuate innate immune dysfunction and activation that underlies HIV pathogenesis, and thus reveal potential new targets for therapy.

Cited by 133 publications

References 63 publications

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

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

Susceptibility to HIV‐1 infection is influenced by toll like receptor‐2 (−196 to −174) polymorphism in a north Indian population

Prophylactic and therapeutic implications of toll‐like receptor ligands

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