Dendritic Cells Pulsed with HIV-1 Release Exosomes that Promote Apoptosis in Cd4+ T Lymphocytes

Subra, Caroline; Simard, Sébastien; Mercier, Simon; Bancila, Aliona; Lambert, Alexandra A.; Graham, David R.; Gilbert, Caroline

doi:10.4172/2155-9899.s7-001

Cited by 12 publications

(29 citation statements)

References 59 publications

(74 reference statements)

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“…We demonstrated in our previous studies that the exosome release from iMDDCs is increased following HIV-1 cell pulsing and that these exosomes have a deleterious effect on neighboring CD4TL (Subra et al, 2011a(Subra et al, , 2011b. However, the role of DCIR in exosome release from HIV-1-pulsed-dendritic cells remains unknown.…”

Section: Impact Of the Dcir-directed Inhibitor On Exosome Release By mentioning

confidence: 89%

“…The latter process appears to lead to trans infection of CD4TL (Izquierdo-Useros et al, 2010). At least one recent study indicates that HIV-1 infection increases exosome secretion by dendritic cells (Subra et al, 2011b). However, it is not yet known if increased exosomes amount by HIV-1-infected cells is DCIR-dependent.…”

Section: Introductionmentioning

confidence: 97%

“…Presence of Nef in exosomes has been shown to cause activation-induced death of resting peripheral blood lymphocytes in vitro (Lenassi et al, 2010). It has also been shown that HIV-1-loaded dendritic cells release exosomes that induce apoptosis in CD4TL (Subra et al, 2011b).…”

Section: Introductionmentioning

confidence: 97%

“…Several studies have shown that CD4TL are depleted first in the gastrointestinal tract during the acute phase of infection (Brenchley et al, 2004;Guadalupe et al, 2003). This is due to the virus itself (Arnoult et al, 2003), to cytotoxic activity of CD8 þ T cells (Sewell et al, 2000) and to cytopathic effects associated with accumulation of abortive HIV-1 reverse transcripts (Doitsh et al, 2010) or extracellular vesicles (EVs) including exosomes (Lenassi et al, 2010;Subra et al, 2011b).…”

Section: Introductionmentioning

confidence: 98%

“…Those derived from dendritic cells are also Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/yviro involved in the development of immune tolerance (Peche et al, 2003;Segura et al, 2005aSegura et al, , 2005b, and via co-stimulatory molecules present on them, in activation of CD4TL (Thery et al, 2002a(Thery et al, , 2002b. In some cases, they appear to contribute to the events leading from HIV-1 infection to AIDS (Lenassi et al, 2010;Subra et al, 2011b).…”

Section: Introductionmentioning

confidence: 98%

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Exosome release following activation of the dendritic cell immunoreceptor: A potential role in HIV-1 pathogenesis

et al. 2015

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Exosomes are extracellular vesicles (EVs) that play a role in intercellular communication. Stimulation of dendritic cells by the HIV-1 virus triggers their release. HIV-1 binds to dendritic cells via dendritic cell immunoreceptor (DCIR). This study shows that inhibiting the binding to DCIR significantly decreases exosome release by HIV-1-pulsed dendritic cells. In addition, exosome release from Raji-CD4 expressing DCIR cells stimulated by anti-DCIR or HIV-1 is decreased when the immunoreceptor tyrosine-based inhibition motif (ITIM) signaling motif of DCIR is mutated. Unlike the EVs released from Raji-CD4-DCIR cells after antibody stimulation, those released from HIV-1-infected cells contain the pro-apoptotic protein DAP-3. Furthermore, EVs from HIV-1 pulsed dendritic cells increase spontaneous apoptosis in uninfected CD4 T lymphocytes while they decrease it in neutrophils. This study describes for the first time that DCIR plays a role in the release of exosomes strengthening the importance of this receptor and EVs/exosomes in HIV-1 pathogenesis.

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Section: Impact Of the Dcir-directed Inhibitor On Exosome Release By mentioning

confidence: 89%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 98%

See 3 more Smart Citations

Exosome release following activation of the dendritic cell immunoreceptor: A potential role in HIV-1 pathogenesis

et al. 2015

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Exosome-associated release, uptake, and neurotoxicity of HIV-1 Tat protein

Rahimian

2016

J. Neurovirol.

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HIV-1 Tat is an indispensible transactivator for HIV gene transcription and replication. It has been shown to exit cells as a free protein and enter neighboring cells or interact with surface receptors of neighboring cells to regulate gene expression and cell function. In this study, we report, for the first time, exosome-associated Tat release and uptake. Using a HIV-1 LTR-driven luciferase reporter-based cell assay and Western blotting or in combination with exosome inhibitor, OptiPrep gradient fractionation, and exosome depletion, we demonstrated significant presence of HIV-1 Tat in exosomes derived from Tat-expressing primary astrocytes, Tat-transfected U373.MG and 293T, and HIV-infected MT4. We further showed that exosome-associated Tat from Tat-expressing astrocytes was capable of causing neurite shortening and neuron death, further supporting that this new form of extracellular Tat is biologically active. Lastly, we constructed a Tat mutant deleted of its basic domain and determined the role of the basic domain in Tat trafficking into exosomes. Basic domain-deleted Tat exhibited no apparent effects on Tat trafficking into exosomes, while maintained its dominant-negative function in Tat-mediated LTR transactivation. Taken together, these results show a significant fraction of Tat is secreted and present in the form of exosomes and may contribute to the stability of extracellular Tat and broaden the spectrum of its target cells.

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Extracellular vesicles and chronic inflammation during HIV infection

Pérez

Romaniuk

Duette

et al. 2019

J of Extracellular Vesicle

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Inflammation is a hallmark of HIV infection. Among the multiple stimuli that can induce inflammation in untreated infection, ongoing viral replication is a primary driver. After initiation of effective combined antiretroviral therapy (cART), HIV replication is drastically reduced or halted. However, even virologically controlled patients may continue to have abnormal levels of inflammation. A number of factors have been proposed to cause inflammation in HIV infection: among others, residual (low‐level) HIV replication, production of HIV protein or RNA in the absence of replication, microbial translocation from the gut to the circulation, co‐infections, and loss of immunoregulatory responses. Importantly, chronic inflammation in HIV‐infected individuals increases the risk for a number of non‐infectious co‐morbidities, including cancer and cardiovascular disease. Thus, achieving a better understanding of the underlying mechanisms of HIV‐associated inflammation in the presence of cART is of utmost importance. Extracellular vesicles have emerged as novel actors in intercellular communication, involved in a myriad of physiological and pathological processes, including inflammation. In this review, we will discuss the role of extracellular vesicles in the pathogenesis of HIV infection, with particular emphasis on their role as inducers of chronic inflammation.

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Dendritic Cells Pulsed with HIV-1 Release Exosomes that Promote Apoptosis in Cd4+ T Lymphocytes

Cited by 12 publications

References 59 publications

Exosome release following activation of the dendritic cell immunoreceptor: A potential role in HIV-1 pathogenesis

Exosome release following activation of the dendritic cell immunoreceptor: A potential role in HIV-1 pathogenesis

Exosome-associated release, uptake, and neurotoxicity of HIV-1 Tat protein

Extracellular vesicles and chronic inflammation during HIV infection

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