20170080_0021

© Hubert RAGUET / Institut Cochin / CNRS Images

Reference

20170080_0021

Dépôt d'une culture de monocytes dans une centrifugeuse

Placing a culture of purified human monocytes from peripheral blood into a centrifuge. These cells will then be differentiated into Langerhans cells, a subpopulation of dendritic cells that presents antigens found in stratified mucosa such as the foreskin or vagina. They will then be infected with HIV or the herpes virus in the laboratory so that they can be used in tests aiming to analyse the molecular mechanisms of infection. Langerhans cells are produced in the laboratory as they are difficult to obtain from tissue, where they are fairly rare. HIV is chiefly transmitted via the genital mucosa during unprotected sexual intercourse. Although the mechanisms through which the virus enters via the female genital mucosa are fairly well understood, much less is known about the way in which the virus enters via the male genital mucosa. That said, epidemiological studies have demonstrated that circumcision is 50 to 70% effective in protecting men from sexually transmitted infection. The "Mucosal entry of HIV and mucosal immunity" team led by Morgane Bomsel has shown that the virus can effectively penetrate the internal surface of the foreskin and rapidly target Langerhans cells, which are antigen-presenting cells that monitor mucosae such as the foreskin. In addition, the mucosae are innervated by peripheral neurons that innervate all mucosae, including the foreskin. These neurons secrete neuropeptides locally following so-called "harmful" stimulation such as heat produced by rubbing. The scientists in the team have demonstrated that one of these locally secreted neuropeptides, calcitonin gene-related peptide (CGRP), blocks HIV from entering mucosae such as the foreskin by stopping it entering the Langerhans cells. This mechanism may also apply to other viruses such as that for genital herpes (HSV), and have consequences for the dynamics of HIV-HSV coinfections. CGRP could therefore serve as a potential natural microbicide.

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