Toll-Like Receptor 2 (TLR2) and TLR9 Signaling Results in HIV-Long Terminal Repeat<i>Trans</i>-Activation and HIV Replication in HIV-1 Transgenic Mouse Spleen Cells: Implications of Simultaneous Activation of TLRs on HIV Replication

Equils, Ozlem; Schito, Marco; Karahashi, Hiase; Madak, Zeynep; Yarali, Ayse; Michelsen, Kathrin S.; Sher, Alan; Arditi, Moshe

doi:10.4049/jimmunol.170.10.5159

Cited by 100 publications

(92 citation statements)

References 59 publications

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“…Once infection had been established (after 18 h), TLR2 and TLR4 were up-regulated in monocytes, probably to maintain the proinflammatory cytokine profile, which can also promote viral replication after provirus formation by activating NF-jB signaling in HIV-1-infected cells, similar to TLRs. [10][11][12][13][14] At the same time, TLR2 expression was downregulated in mDCs, the most important antigen-presenting cells, suggesting a viral mechanism to evade the immune response. 19 Thus, TLR activation may promote HIV-1 infection due to the effect of downstream signaling effectors on viral replication.…”

Section: Discussionmentioning

confidence: 89%

“…Subsequently, NF-jB can activate the HIV-1 genome by binding to the viral long terminal repeats (LTRs) in the provirus, even in models of HIV-1 latency. [10][11][12][13][14][15] TLRs are expressed in HIV-1 reservoir cells such as CD4 + T cells, macrophages, and DCs. [16][17][18][19] Various reports indicated that HIV-derived RNA can activate pDCs via TLR7 and TLR8.…”

Section: Introductionmentioning

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.…”

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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: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

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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“…Diferentes estudios sugieren que las infecciones por patógenos oportunistas, además de reducir la supervivencia de los pacientes con sida, al incidir directamente en la mortalidad, también representan un coestímulo para acelerar la pérdida de la función inmune y la progresión de la infección (6,7). De hecho, la presencia de infecciones oportunistas se ha asociado con activación de las células del sistema inmune, algunas de ellas infectadas con el VIH-1, promoviendo la replicación viral (8,9).…”

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“…De hecho, la presencia de infecciones oportunistas se ha asociado con activación de las células del sistema inmune, algunas de ellas infectadas con el VIH-1, promoviendo la replicación viral (8,9). Esto se traduce en un incremento de la carga viral en la circulación sistémica y en los diferentes tejidos (8), además de favorecer la diseminación de la infección, la apoptosis de varias subpoblaciones de células y la aparición de mutaciones en el genoma viral (7,10). Todo esto posibilita la evasión de la respuesta inmune y se puede asociar con cambios en el tropismo, en la patogenicidad, con la aparición de cepas resistentes a la terapia antirretroviral (2,11,12).…”

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Efecto de las infecciones oportunistas sobre las subpoblaciones de leucocitos en individuos infectados con el virus de inmunodeficiencia humana tipo 1

et al. 2008

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Introducción. La presencia de infecciones por patógenos oportunistas en pacientes con síndrome de inmunodeficiencia adquirida representa un coestímulo para acelerar la progresión de la infección por el VIH-1. A pesar del papel preponderante que varias subpoblaciones de leucocitos tienen en la respuesta antiinfecciosa, poco se ha estudiado el comportamiento de esas células en pacientes positivos para VIH-1 que presentan infecciones oportunistas. Objetivo. Evaluar cuantitativamente las subpoblaciones celulares más importantes de la inmunidad innata y adaptativa en sangre periférica de adultos infectados con el VIH-1 (con antecedentes de infecciones oportunistas y sin ellos). Materiales y métodos. El número absoluto de las diferentes subpoblaciones de leucocitos fue determinado por citometría de flujo; para cada subpoblación, este número se correlacionó con la carga viral, el recuento de linfocitos T CD4+ y la expresión de marcadores de activación inmunológica en células T CD4+ y CD8+. Resultados. Los pacientes crónicamente infectados por el VIH-1 presentan deficiencia cuantitativa de varias subpoblaciones de leucocitos, que es más significativa en aquellos pacientes con una infección oportunista activa al momento de la evaluación, lo cual indica que la coinfección VIH-1/agentes oportunistas puede potenciar la inmunodeficiencia al asociarse con una reducción significativa de las diferentes subpoblaciones de leucocitos. Conclusiones. Estos hallazgos sugieren la necesidad de hacer un diagnóstico temprano de la infección por el VIH-1 y un uso racional de la terapia antirretroviral de manera que se impida que los pacientes lleguen a desarrollar infecciones oportunistas, así como la necesidad de establecer estrategias de inmunoterapia para pacientes positivos para VIH-1 con el fin de reestablecer más integralmente la competencia inmune.Palabras clave: infecciones oportunistas relacionadas con sida/inmunología, leucocitos, VIH-1, activación de linfocitos, células dendríticas, células asesinas naturales. Effect of opportunistic infections on the frequency of leukocyte subpopulations from type-1 human immunodeficiency virus infected individualsIntroduction. The presence of opportunistic infections in patients with acquired immunodeficiency syndrome favors the progression of HIV-1 infection. Despite the key role that several leukocyte subpopulations exhibit during the anti-infectious response, few studies have focused on the role of these cells in HIV-1-infected patients with active opportunistic infections. Objective. The quantity of several innate and adaptive cell subpopulations was evaluated in whole peripheral blood of HIV-1-infected patients, with and without a history of opportunistic infections. Materials and methods. The absolute number of each leukocyte subpopulation was evaluated by flow cytometry, and for each cell subpopulation, this number was correlated with viral load, CD4+ T cell count and the expression of activation markers on CD4+ and CD8+ T lymphocytes. Results. Chronically HIV-1 infected patients exhib...

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Tuberculosis/Human Immunodeficiency Virus Coinfection and the Host Immune Response

Goldfeld¹,

Tsitsikov²

2008

Handbook of Tuberculosis

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Toll-Like Receptor 2 (TLR2) and TLR9 Signaling Results in HIV-Long Terminal RepeatTrans-Activation and HIV Replication in HIV-1 Transgenic Mouse Spleen Cells: Implications of Simultaneous Activation of TLRs on HIV Replication

Cited by 100 publications

References 59 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

Efecto de las infecciones oportunistas sobre las subpoblaciones de leucocitos en individuos infectados con el virus de inmunodeficiencia humana tipo 1

Tuberculosis/Human Immunodeficiency Virus Coinfection and the Host Immune Response

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