Up-Regulation of TLR2 and TLR4 in Dendritic Cells in Response to HIV Type 1 and Coinfection with Opportunistic Pathogens

Hernández, Juan Carlos; Arteaga, H. José; Paul, Stéphane; Kumar, Ajit; Latz, Eicke; Urcuqui-Inchima, Silvio

doi:10.1089/aid.2010.0302

Cited by 47 publications

(58 citation statements)

References 52 publications

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“…1). As previously reported, 34 flow cytometry and real time RT-PCR show that pDCs can express TLR2 and TLR4, suggesting an important role of these receptors in activating antiviral responses in the pDCs subsets as well as the induction of type I IFN production. Indeed, using functional assays, pDCs were shown to increase the expression of the costimulatory molecule CD80 in response to TLR2 and TLR4 stimulation (Fig.…”

Section: Discussionsupporting

confidence: 80%

“…29 Lately, we have also reported that TLR2 and TLR4 expression is increased in DCs from HIV-1-infected patients with opportunistic infections. 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.…”

Section: Discussionmentioning

confidence: 99%

“…Logical gating was used to identify monocyte (CD14 + ), pDCs (BDCA-2 + /CD123 high ), and mDCs (Lin1 -/CD11c high ) populations. 34 For DC evaluation, at least 200,000 gated events were acquired and at least 150,000 gated events for monocytes. The acquired events were analyzed using CellQuest software.…”

Section: Flow Cytometry Analysismentioning

confidence: 99%

“…34 In the present study, we determined the expression levels of the TLR2 and TLR4 proteins and mRNAs to assess whether HIV-1 infection alters TLR expression on antigen-presenting cells. TLR2 expression was increased in monocytes and mDCs ( p < 0.01 and p < 0.05, respectively) from HIV-1-infected patients compared to healthy donors (Fig.…”

mentioning

confidence: 99%

“…These results are in line with our previous findings in HIV-1-infected patients with opportunistic infections, who also have higher TLR2 and TLR4 levels in DCs. 34 This could be associated with a higher viral load since TLRs can mediate the activation of HIV-1 LTR through the NF-jB pathway, 10,11,14 suggesting than TLR expression levels could be influenced by viral factors and by the immunological state of the host.…”

mentioning

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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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Flow Cytometry Analysismentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

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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Alteration of T Cell Phenotypes in HIV‐Neurotuberculosis Coinfection

Rao

Venkataswamy

Ravi

et al. 2018

Cytometry Part B Clinical

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Background Neurotuberculosis is one of the commonest HIV associated opportunistic infections of the central nervous system in India. HIV‐TB coinfection may lead to altered frequencies of T cells, thereby influencing the course and progression of the disease. Methods We examined the frequencies of T cell subsets in HIV infected individuals with neurotuberculosis (HIV+nTB+) as compared to individuals with HIV associated systemic TB (HIV+sTB+), asymptomatic HIV (HIV+TB‐), non‐HIV neuro TB (HIV‐nTB+), non‐HIV systemic TB (HIV‐sTB+), and healthy controls (HIV‐TB‐). Activation and senescence profiles of CD4 and CD8 T cells and memory subsets in peripheral blood mononuclear cells were studied by flow cytometry. Results The significant observations among the T cell subsets in HIV+nTB+ were: (1) Naïve T cells: decreased CD4 T cells compared to HIV‐sTB+ (P = 0.005); decreased CD8 T cells compared to HIV‐nTB+ and HIV‐TB‐ (P ≤ 0.007), (2) Memory T cells: expanded CD4 TEMRA cells compared to HIV‐nTB+, HIV‐sTB+, and HIV‐TB‐ (P ≤ 0.003); expanded CD8 TEMRA cells compared to HIV‐nTB+ and HIV‐TB‐ (P ≤ 0.005), (3) Activated T cells: higher CD4 T cells compared to HIV‐nTB+, HIV‐sTB+, and HIV‐TB‐ (P ≤ 0.004); higher CD8 T cells compared to HIV + TB‐, HIV‐nTB+, HIV‐sTB+, and HIV‐TB‐ (P ≤ 0.001), and (4) Senescent T cells: increased CD8 T cells compared to HIV‐nTB+ and HIV‐TB‐ groups (P = 0.000). Conclusions Increased activation compared to HIV+TB‐, HIV‐nTB+, HIV‐sTB+, and HIV‐TB‐ groups and increased senescence compared to HIV‐nTB+ and HIV‐TB‐ groups were observed in CD8 T cells in HIV+nTB+, suggesting that the frequencies of these T cell subsets are altered to a greater extent in these individuals. © 2018 International Clinical Cytometry Society

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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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Up-Regulation of TLR2 and TLR4 in Dendritic Cells in Response to HIV Type 1 and Coinfection with Opportunistic Pathogens

Cited by 47 publications

References 52 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

Alteration of T Cell Phenotypes in HIV‐Neurotuberculosis Coinfection

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

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