CGRP inhibits human Langerhans cells infection with HSV by differentially modulating specific HSV-1 and HSV-2 entry mechanisms

Cohen, Emmanuel; Mariotton, Jammy; Rozenberg, Flore; Sams, Anette; Kuppevelt, Toin H. Van; Delongchamps, Nicolas Barry; Zerbib, Marc; Bomsel, Morgane; Ganor, Yonatan

doi:10.1038/s41385-022-00521-y

Cited by 6 publications

(4 citation statements)

References 47 publications

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“…Next, Calu-3 cells were pre-treated for 24h at 37°C with CGRP within its concentration range that inhibits LCs-mediated HIV-1 and HSV-1/2 infection, as we reported (29,30). The cells were also pre-treated with the CGRP metabolically stable analogue SAX (serinyl-CGRP 2-37amide with an albumin binding fatty acid moiety in the N-terminus) that, like CGRP, exerts protective cardiovascular effects (37)(38)(39)(40) and anti-viral functions (29,30), as we reported. The cells were next washed, pulsed with SARS-CoV-2 variants for 4h, and infection was determined by flow cytometry as above.…”

Section: Cgrp and Its Analogue Sax Inhibit Sars-cov-2 Infection Of Ca...mentioning

confidence: 99%

“…In particular, CGRP: i) enhances surface expression of atypical double-trimmers of the LC-specific pathogen-recognition lectin langerin, i.e. the receptor of both HIV-1/HSV-2, resulting in reduced viral capture (30); ii) decreases surface expression of the HIV-1 entry co-receptor CCR5 (27), and the HSV-1 entry receptor 3-O sulfated heparan sulfate (30).…”

Section: Introductionmentioning

confidence: 99%

“…Besides its immunomodulatory and vasodilatory roles, CGRP also exerts anti-viral functions, as we previously discovered (26)(27)(28)(29)(30). Indeed, CGRP strongly inhibits infection of antigenpresenting Langerhans cells (LCs) with human immunodeficiency virus type 1 (HIV-1) and herpes simplex virus types 1 and 2 (HSV-1/2) (26)(27)(28)(29)(30). One shared CGRP-mediated anti-viral mechanism involves modulation of surface expression of different viral attachment and entry receptors.…”

Section: Introductionmentioning

confidence: 99%

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CGRP inhibits SARS-CoV-2 infection of bronchial epithelial cells and its pulmonary levels correlate with viral clearance in critical COVID-19 patients

Barbosa Bomfim,

Genin,

Cottoignies-Callamarte

et al. 2024

Preprint

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Upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), patients with critical coronavirus disease 2019 (COVID-19) present with life-threatening respiratory distress, pulmonary damage and cytokine storm. One unexplored hub in COVID-19 is the neuropeptide calcitonin gene-related peptide (CGRP), which is highly abundant in the airways and could converge in multiple aspects of COVID-19-related pulmonary pathophysiology. Whether CGRP affects SARS-CoV-2 infection directly remains elusive. We show that in critical COVID-19 patients, CGRP is increased in both plasma and lungs. Importantly, CGRP pulmonary levels are elevated in early SARS-CoV-2-positive patients, and restore to baseline upon subsequent viral clearance in SARS-CoV-2-negative patients. We further show that CGRP and its stable analogue SAX directly inhibit infection of bronchial Calu-3 epithelial cells with SARS-CoV-2 Omicron and Alpha variants in a dose-dependent manner. Both pre- and post-infection treatment with GRRP and/or SAX is enough to block SARS-CoV-2 productive infection of Calu3 cells. CGRP-mediated inhibition occurs via activation of the CGRP receptor and involves down-regulation of SARS-CoV-2 entry receptors at the surface of Calu-3 cells. Together, we propose that increased pulmonary CGRP mediates beneficial viral clearance in critical COVID-19 patients, by directly inhibiting SARS-CoV-2 infection. Hence, CGRP-based interventions could be harnessed for management of COVID-19.Brief summaryPulmonary levels of the neuropeptide CGRP are increased in critical COVID-19 patients, and could clear virus by directly inhibiting SRAS-CoV-2 infection of bronchial epithelia cells.

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Section: Cgrp and Its Analogue Sax Inhibit Sars-cov-2 Infection Of Ca...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CGRP inhibits SARS-CoV-2 infection of bronchial epithelial cells and its pulmonary levels correlate with viral clearance in critical COVID-19 patients

Barbosa Bomfim,

Genin,

Cottoignies-Callamarte

et al. 2024

Preprint

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“…52,122 Neuropeptides, such as calcitonin gene-related peptide (CGRP) and substance P, released from sensory nerve fibres are gaining increasing traction as modulators of bidirectional interactions between cutaneous nerve fibres and myeloid cells such as LCs, including their role in neurogenic inflammation. 28,32,62,151 Calcitonin gene-related peptide released from optogenetically activated TRPV1 + nerve fibres in mouse skin induces CD301b + dermal DCs to activate γδ T cells in a process known as “anticipatory immunity.” 29 Mast cells are also implicated in mediating inflammatory pain through the release of substance P by TRPV1 + neurons, causing mast cell degranulation, proinflammatory cytokine release, and peripheral immune cell recruitment. 57,169 MrgprD-expressing neurons also release glutamate to promote cutaneous neuroimmune homeostasis and prevent mast cell hyperresponsiveness.…”

Section: Introductionmentioning

confidence: 99%

Nerve–myeloid cell interactions in persistent human pain: a reappraisal using updated cell subset classifications

O'Brien,

Karrasch,

Huang

et al. 2023

Pain

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The past 20 years have seen a dramatic shift in our understanding of the role of the immune system in initiating and maintaining pain. Myeloid cells, including macrophages, dendritic cells, Langerhans cells, and mast cells, are increasingly implicated in bidirectional interactions with nerve fibres in rodent pain models. However, our understanding of the human setting is still poor. High-dimensional functional analyses have substantially changed myeloid cell classifications, with recently described subsets such as epidermal dendritic cells and DC3s unveiling new insight into how myeloid cells interact with nerve fibres. However, it is unclear whether this new understanding has informed the study of human chronic pain. In this article, we perform a scoping review investigating neuroimmune interactions between myeloid cells and peripheral nerve fibres in human chronic pain conditions. We found 37 papers from multiple pain states addressing this aim in skin, cornea, peripheral nerve, endometrium, and tumour, with macrophages, Langerhans cells, and mast cells the most investigated. The directionality of results between studies was inconsistent, although the clearest pattern was an increase in macrophage frequency across conditions, phases, and tissues. Myeloid cell definitions were often outdated and lacked correspondence with the stated cell types of interest; overreliance on morphology and traditional structural markers gave limited insight into the functional characteristics of investigated cells. We therefore critically reappraise the existing literature considering contemporary myeloid cell biology and advocate for the application of established and emerging high-dimensional proteomic and transcriptomic single-cell technologies to clarify the role of specific neuroimmune interactions in chronic pain.

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Epithelial dendritic cells vs. Langerhans cells: Implications for mucosal vaccines

Vine,

Austin,

O’Neil

et al. 2024

Cell Reports

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CGRP inhibits human Langerhans cells infection with HSV by differentially modulating specific HSV-1 and HSV-2 entry mechanisms

Cited by 6 publications

References 47 publications

CGRP inhibits SARS-CoV-2 infection of bronchial epithelial cells and its pulmonary levels correlate with viral clearance in critical COVID-19 patients

CGRP inhibits SARS-CoV-2 infection of bronchial epithelial cells and its pulmonary levels correlate with viral clearance in critical COVID-19 patients

Nerve–myeloid cell interactions in persistent human pain: a reappraisal using updated cell subset classifications

Epithelial dendritic cells vs. Langerhans cells: Implications for mucosal vaccines

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