Objectif Worldwide a large proportion of all new cases of HIV-1 infection are due to anal sexual intercourse, being the anal/rectal as well as distal colonic mucosa a site of viral uptake and entry. I recently demonstrated that intestinal lamina propria resident DCs migrate towards and extend cellular processes between the tight junctions of columnar epithelium through a CCR5-dependent mechanism, take up R5 but not X4 HIV-1, and then transfer infection to susceptible T cells. Although in mice CX3CR1+DCs are deputed to shuttle microbial antigens, there is no clear idea on which subsets of DCs are located in the human GI tract, are involved in HIV infection and contribute to virus spread, its presentation or possibly to its reservoir. Moreover, the ability of DCs to shuttle the virus across the mucosa may be largely modulated by components of semen, the natural vehicle of HIV during sexual transmission.To fill these gaps I propose a comparative study in macaques and humans using a multidisciplinary approach, which will unravel the mechanism associated with rectal transmission of HIV/SIV by DCs and their modulation by semen. Specific objectives will be:1. Define the subsets of DCs and the molecular mechanism(s) through which DCs directly sample HIV-1/SIV through the intestinal epithelium and facilitate the spread of the infection.2. Define the impact of semen on HIV/SIV-induced DCs migration across the epithelium.3. Determine the ability of lamina propria DCs subsets to migrate across the intestinal epithelium and to redistribute to draining lymph-nodes following in vivo exposure of Cynomolgus macaques to infectious pathogenic SIV.We expect to characterize the early events of DC-mediated intestinal transmission of HIV/SIV and thus contribute to the knowledge base needed to identify, evaluate and develop novel agents or strategies to prevent mucosal HIV transmission Champ scientifique natural sciencesbiological scienceszoologymammalogyprimatologynatural sciencesbiological sciencesmicrobiologyvirologymedical and health scienceshealth sciencesinfectious diseasesRNA virusesHIVnatural sciencesphysical sciencesopticsmicroscopyconfocal microscopy Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Thème(s) MSCA-IF-2014-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Appel à propositions H2020-MSCA-IF-2014 Voir d’autres projets de cet appel Régime de financement MSCA-IF-EF-ST - Standard EF Coordinateur COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES Contribution nette de l'UE € 173 076,00 Adresse RUE LEBLANC 25 75015 PARIS 15 France Voir sur la carte Région Ile-de-France Ile-de-France Paris Type d’activité Research Organisations Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 173 076,00
