scholarly journals Calcitonin gene–related peptide inhibits Langerhans cell–mediated HIV-1 transmission

2013 ◽  
Vol 210 (11) ◽  
pp. 2161-2170 ◽  
Author(s):  
Yonatan Ganor ◽  
Anne-Sophie Drillet-Dangeard ◽  
Lucia Lopalco ◽  
Daniela Tudor ◽  
Giuseppe Tambussi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Highly Active Antiretroviral Therapy ◽  
Plasma Levels ◽  
Calcitonin Gene Related Peptide ◽  
Cell Infection ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Hiv 1

Upon its mucosal entry, human immunodeficiency virus type 1 (HIV-1) is internalized by Langerhans cells (LCs) in stratified epithelia and transferred locally to T cells. In such epithelia, LCs are in direct contact with peripheral neurons secreting calcitonin gene–related peptide (CGRP). Although CGRP has immunomodulatory effects on LC functions, its potential influence on the interactions between LCs and HIV-1 is unknown. We show that CGRP acts via its receptor expressed by LCs and interferes with multiple steps of LC-mediated HIV-1 transmission. CGRP increases langerin expression, decreases selected integrins, and activates NF-κB, resulting in decreased HIV-1 intracellular content, limited formation of LC–T cell conjugates, and elevated secretion of the CCR5-binding chemokine CCL3/MIP-1α. These mechanisms cooperate to efficiently inhibit HIV-1 transfer from LCs to T cells and T cell infection. In vivo, HIV-1 infection decreases CGRP plasma levels in both vaginally SHIV-challenged macaques and HIV-1–infected individuals. CGRP plasma levels return to baseline after highly active antiretroviral therapy. Our results reveal a novel path by which a peripheral neuropeptide acts at the molecular and cellular levels to limit mucosal HIV-1 transmission and suggest that CGRP receptor agonists might be used therapeutically against HIV-1.

scholarly journals Calcitonin Gene-Related Peptide Induces HIV-1 Proteasomal Degradation in Mucosal Langerhans Cells

2017 ◽  
Vol 91 (23) ◽  
Author(s):  
Morgane Bomsel ◽  
Yonatan Ganor
Keyword(s):  
T Cells ◽  
Langerhans Cells ◽  
Sexual Transmission ◽  
Proteasomal Degradation ◽  
Sexual Response ◽  
Peripheral Neurons ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Hiv 1

ABSTRACT The neuroimmune dialogue between peripheral neurons and Langerhans cells (LCs) within mucosal epithelia protects against incoming pathogens. LCs rapidly internalize human immunodeficiency virus type 1 (HIV-1) upon its sexual transmission and then trans-infect CD4+ T cells. We recently found that the neuropeptide calcitonin gene-related peptide (CGRP), secreted mucosally from peripheral neurons, inhibits LC-mediated HIV-1 trans-infection. In this study, we investigated the mechanism of CGRP-induced inhibition, focusing on HIV-1 degradation in LCs and its interplay with trans-infection. We first show that HIV-1 degradation occurs in endolysosomes in untreated LCs, and functionally blocking such degradation with lysosomotropic agents results in increased trans-infection. We demonstrate that CGRP acts via its cognate receptor and at a viral postentry step to induce faster HIV-1 degradation, but without affecting the kinetics of endolysosomal degradation. We reveal that unexpectedly, CGRP shifts HIV-1 degradation from endolysosomes toward the proteasome, providing the first evidence for functional HIV-1 proteasomal degradation in LCs. Such efficient proteasomal degradation significantly inhibits the first phase of trans-infection, and proteasomal, but not endolysosomal, inhibitors abrogate CGRP-induced inhibition. Together, our results establish that CGRP controls the HIV-1 degradation mode in LCs. The presence of endogenous CGRP within innervated mucosal tissues, especially during the sexual response, to which CGRP contributes, suggests that HIV-1 proteasomal degradation predominates in vivo. Hence, proteasomal, rather than endolysosomal, HIV-1 degradation in LCs should be enhanced clinically to effectively restrict HIV-1 trans-infection. IMPORTANCE During sexual transmission, HIV-1 is internalized and degraded in LCs, the resident antigen-presenting cells in mucosal epithelia. Yet during trans-infection, infectious virions escaping degradation are transferred to CD4+ T cells, the principal HIV-1 targets. We previously found that the neuroimmune dialogue between LCs and peripheral neurons, innervating mucosal epithelia, significantly inhibits trans-infection via the action of the secreted neuropeptide CGRP on LCs. In this study, we investigated whether CGRP-induced inhibition of trans-infection is linked to CGRP-controlled HIV-1 degradation in LCs. We show that in untreated LCs, HIV-1 is functionally degraded in endolysosomes. In sharp contrast, we reveal that in CGRP-treated LCs, HIV-1 is diverted toward and degraded via another cytosolic protein degradative pathway, namely, the proteasome. These results establish that CGRP regulates HIV-1 degradation in LCs. As CGRP contributes to the sexual response and present within mucosal epithelia, HIV-1 proteasomal degradation in LCs might predominate in vivo and should be enhanced clinically.

Induction of insulin resistance in vivo by amylin and calcitonin gene-related peptide

Diabetes ◽  
1990 ◽  
Vol 39 (2) ◽  
pp. 260-265 ◽  
Author(s):  
J. M. Molina ◽  
G. J. Cooper ◽  
B. Leighton ◽  
J. M. Olefsky
Keyword(s):  
Insulin Resistance ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Calcitonin Gene

scholarly journals Interleukin 7 Increases Human Immunodeficiency Virus Type 1 LAI-Mediated Fas-Induced T-Cell Death

2005 ◽  
Vol 79 (5) ◽  
pp. 3195-3199 ◽  
Author(s):  
Jean-Daniel Lelièvre ◽  
Frédéric Petit ◽  
Damien Arnoult ◽  
Jean-Claude Ameisen ◽  
Jérôme Estaquier
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
Hiv Infection ◽  
Cell Infection ◽  
Interleukin 7 ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Fas-mediated T-cell death is known to occur during human immunodeficiency virus (HIV) infection. In this study, we found that HIV type 1 LAI (HIV-1LAI) primes CD8+ T cells from healthy donors for apoptosis, which occurs after Fas ligation. This effect is counteracted by a broad caspase inhibitor (zVAD-fmk). Fas-mediated cell death does not depend on CD8+ T-cell infection, because it occurred in the presence of reverse transcriptase inhibitors. However, purified CD8+ T cells are sensitive to Fas only in the presence of soluble CD4. Finally, we found that interleukin 7 (IL-7) increases Fas-mediated CD4+ and CD8+ T-cell death induced by HIV-1LAI. Since high levels of IL-7 are a marker of poor prognosis during HIV infection, our data suggest that enhancement of Fas-mediated T-cell death by HIV-1LAI and IL-7 is one of the mechanisms involved in progression to AIDS.

scholarly journals Infection of CD8+CD45RO+ Memory T-Cells by HIV-1 and Their Proliferative Response

2008 ◽  
Vol 2 (1) ◽  
pp. 43-57 ◽  
Author(s):  
Naveed Gulzar ◽  
Sowyma Balasubramanian ◽  
Greg Harris ◽  
Jaime Sanchez-Dardon ◽  
Karen F.T. Copeland
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Proliferative Response ◽  
Cell Infection ◽  
Cellular Target ◽  
Potential Reservoir ◽  
Infected Cells ◽  
Hiv 1

CD8+ T-cells are involved in controlling HIV-1 infection by eliminating infected cells and secreting soluble factors that inhibit viral replication. To investigate the mechanism and significance of infection of CD8+ T-cells by HIV-1in vitro, we examined the susceptibility of these cells and their subsets to infection. CD8+ T-cells supported greater levels of replication with T-cell tropic strains of HIV-1, though viral production was lower than that observed in CD4+ T-cells. CD8+ T-cell infection was found to be productive through ELISA, RT-PCR and flow cytometric analyses. In addition, the CD8+CD45RO+ memory T-cell population supported higher levels of HIV-1 replication than CD8+CD45RA+ naïve T-cells. However, infection of CD8+CD45RO+ T-cells did not affect their proliferative response to the majority of mitogens tested. We conclude, with numerous lines of evidence detecting and measuring infection of CD8+ T-cells and their subsets, that this cellular target and potential reservoir may be central to HIV-1 pathogenesis.

scholarly journals TAILORED DC INDUCE PROTECTIVE HIV-1 SPECIFIC POLYFUNCTIONAL CD8+ T CELLS IN THE LYMPHOID TISSUE FROM HUMANIZED BLT MICE

2021 ◽  
Author(s):  
Marta Calvet-Mirabent ◽  
Daniel T. Claiborne ◽  
Maud Deruaz ◽  
Serah Tanno ◽  
Carla Serra ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Lymphoid Tissue ◽  
White Pulp ◽  
Blt Mice ◽  
Secondary Lymphoid Organs ◽  
The Impact ◽  
Hiv 1

Effective function of CD8+ T cells and enhanced innate activation of dendritic cells (DC) in response to HIV-1 is linked to protective antiviral immunity in controllers. Manipulation of DC targeting the master regulator TANK-binding Kinase 1 (TBK1) might be useful to acquire controller-like properties. Here, we evaluated the impact of TBK1-primed DC inducing protective CD8+ T cell responses in lymphoid tissue and peripheral blood and their association with reduced HIV-1 disease progression in vivo in the humanized bone marrow, liver and thymus (hBLT) mouse model. A higher proportion of hBLT-mice vaccinated with TBK1-primed DC exhibited less severe CD4+ T cell depletion following HIV-1 infection compared to control groups. This was associated with infiltration of CD8+ T cells in the white pulp from the spleen, reduced spread of infected p24+ cells to secondary lymphoid organs and with preserved abilities of CD8+ T cells from the spleen and blood of vaccinated animals to induce specific polyfunctional responses upon antigen stimulation. Therefore, TBK1-primed DC might be an useful tool for subsequent vaccine studies.

Plasma levels of calcitonin gene-related peptide in chronic tension-type headache

Neurology ◽  
2000 ◽  
Vol 55 (9) ◽  
pp. 1335-1340 ◽  
Author(s):  
M. Ashina ◽  
L. Bendtsen ◽  
R. Jensen ◽  
S. Schifter ◽  
I. Jansen-Olesen ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Calcitonin Gene Related Peptide ◽  
Tension Type Headache ◽  
Chronic Tension Type Headache ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Type Headache

scholarly journals Induction of Insulin Resistance In Vivo by Amylin and Calcitonin Gene-Related Peptide

Diabetes ◽  
1990 ◽  
Vol 39 (2) ◽  
pp. 260-265 ◽  
Author(s):  
J. M. Molina ◽  
G. J. S. Cooper ◽  
B. Leighton ◽  
J. M. Olefsky
Keyword(s):  
Insulin Resistance ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Calcitonin Gene
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