Langerhans cells and sexual transmission of <scp>HIV</scp> and <scp>HSV</scp>

Botting, Rachel A.; Rana, Hafsa; Bertram, Kirstie M.; Rhodes, Jake W.; Baharlou, Heeva; Nasr, Najla; Cunningham, Anthony L.; Harman, Andrew N.

doi:10.1002/rmv.1923

Cited by 26 publications

(22 citation statements)

References 119 publications

(211 reference statements)

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“…Mucosal surfaces are the first entry site for HIV during transmission (Figure 1). Indeed, Langerhans cells (LCs), urethral macrophages and/or conventional DCs residing in mucosal tissues have been proposed to capture HIV (178)(179)(180)(181)(182)(183)(184)(185) and further replicate or transfer the virus locally to potential HIV target cells, such as macrophages and CD4 + T cells (Figure 1). NK cells, macrophages and DCs, which are the effector cells involved in Fc-mediated Ab functions, are present in different mucosal tissues at different levels.…”

Section: Roles Of Fc-mediated Antibody Functions In Mucosal Tissuesmentioning

confidence: 99%

Update on Fc-Mediated Antibody Functions Against HIV-1 Beyond Neutralization

Dispinseri

Iannone

et al. 2019

Front. Immunol.

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Antibodies (Abs) are the major component of the humoral immune response and a key player in vaccination. The precise Ab-mediated inhibitory mechanisms leading to in vivo protection against HIV have not been elucidated. In addition to the desired viral capture and neutralizing Ab functions, complex Ab-dependent mechanisms that involve engaging immune effector cells to clear infected host cells, immune complexes, and opsonized virus have been proposed as being relevant. These inhibitory mechanisms involve Fc-mediated effector functions leading to Ab-dependent cellular cytotoxicity, phagocytosis, cell-mediated virus inhibition, aggregation, and complement inhibition. Indeed, the decreased risk of infection observed in the RV144 HIV-1 vaccine trial was correlated with the production of non-neutralizing inhibitory Abs, highlighting the role of Ab inhibitory functions besides neutralization. Moreover, Ab isotypes and subclasses recognizing specific HIV envelope epitopes as well as pecular Fc-receptor polymorphisms have been associated with disease progression. These findings further support the need to define which Fc-mediated Ab inhibitory functions leading to protection are critical for HIV vaccine design. Herein, based on our previous review Su & Moog Front Immunol 2014, we update the different inhibitory properties of HIV-specific Abs that may potentially contribute to HIV protection.

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Section: Roles Of Fc-mediated Antibody Functions In Mucosal Tissuesmentioning

confidence: 99%

Update on Fc-Mediated Antibody Functions Against HIV-1 Beyond Neutralization

Dispinseri

Iannone

et al. 2019

Front. Immunol.

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“…H IV-1 invades the body principally during unprotected sexual intercourse and is rapidly internalized by resident Langerhans cells (LCs) in the male (1,2) and female (3) genital epithelia. Depending on the LC preparation/isolation method (4) and HIV-1 load (5), and especially ex vivo (1)(2)(3), infectious virions might be retained by LCs within tetraspanin-rich intracellular compartments (6) and then transferred to CD4 ϩ T cells during the first phase of a process termed trans-infection (7). Although HIV-1 productive infection of LCs is limited (8,9), virions produced de novo are additionally transferred later, during the second phase of trans-infection (7).…”

mentioning

confidence: 99%

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

Bomsel

Ganor

2017

J Virol

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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 -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 -infection. In this study, we investigated the mechanism of CGRP-induced inhibition, focusing on HIV-1 degradation in LCs and its interplay with-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 -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-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 Hence, proteasomal, rather than endolysosomal, HIV-1 degradation in LCs should be enhanced clinically to effectively restrict HIV-1-infection. During sexual transmission, HIV-1 is internalized and degraded in LCs, the resident antigen-presenting cells in mucosal epithelia. Yet during -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 -infection via the action of the secreted neuropeptide CGRP on LCs. In this study, we investigated whether CGRP-induced inhibition of-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 and should be enhanced clinically.

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“…Anthony L. Cunningham (University of Sydney, Australia) described the "find me" and "eat me" signals that attract human dermal dendritic cells (dDCs) to Langerhans cells (LCs) infected with herpes simplex virus (HSV), and facilitate recognition and uptake of apoptotic LCs (Botting et al, 2017). He and his colleagues assessed the expression of chemokines by HSV-infected LCs and corresponding chemokine receptors on dDC subsets, as well as apoptotic receptors that may recognize and facilitate their interactions.…”

Section: Persistent Virusesmentioning

confidence: 99%

2017 international meeting of the Global Virus Network

et al. 2018

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The Global Virus Network (GVN) was established in 2011 to strengthen research and responses to emerging viral causes of human disease and to prepare against new viral pandemics. There are now 40 GVN Centers of Excellence and 6 Affiliate laboratories in 24 countries. The 2017 meeting was held from September 25-27 in Melbourne, Australia, and was hosted by the Peter Doherty Institute for Infection and Immunity and the Institut Pasteur. This report highlights the recent accomplishments of GVN researchers in several important areas of medical virology, including the recent Zika epidemic, infections by human papillomavirus, influenza, HIV, hepatitis C, HTLV-1, and chikungunya viruses, and new and emerging viruses in the Australasia region. Plans for the 2018 meeting also are noted.

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Langerhans cells and sexual transmission of HIV and HSV

Cited by 26 publications

References 119 publications

Update on Fc-Mediated Antibody Functions Against HIV-1 Beyond Neutralization

Update on Fc-Mediated Antibody Functions Against HIV-1 Beyond Neutralization

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

2017 international meeting of the Global Virus Network

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