Tuberculosis boosts HIV-1 infection of macrophages by triggering IL-10/STAT3-dependent tunneling nanotube formation

SOURIANT S; BALBOA L; PRINGIS K; KVIATCOVSKY D; COUGOULE C; LASTRUCCI C; BAH A; GASSER R; POINCLOUX R; RAYNAUD-MESSINA B; TALAL AL SAATI; INWENTARZ S; POGGI S; MORAÑA E; GONZÁLEZ MONTANER P; CORTI M; LAGANE B; VERGNE I; ALLERS C; KAUSHAL D; KURODA M; SASIAIN MC; NEYROLLES O; MARIDONNEAU-PARINI I; LUGO-VILLARINO G; VEROLLET C

Congreso; 41st Annual International Dictyostelium Conference; 2017

Mycobacterium tuberculosis (Mtb) and HIV 1 are known to act synergistically and impact the progression of one another in co infected patients. Yet, the mechanisms by which Mtb exacerbates HIV 1 pathogenesis remain poorly characterized. Here, we show that Mtb infection enhances HIV 1 production in macrophages. This phenomenon does not rely on increased viral receptor-mediated entry or early replication, nor on the down-regulation of HIV restriction factors in macrophages. Instead, we report for the first time that Mtb infection triggers the formation of tunneling nanotubes (TNTs) which increase cell to cell viral spread. Strikingly, blocking IL 10, the IL 10/STAT3 signaling platform or TNT formation itself, fully abolished enhanced HIV 1 production by macrophages in a TB associated microenvironment. We also found that such virus overproducing macrophages belong to an M(IL 10) anti inflammatory macrophage program, and are expanded in the peripheral blood of co infected patients and in the lungs of co infected non human primates; accumulation of this macrophage population correlates with disease severity. Altogether, our data identify TNTs induced during Mtb infection of macrophages as key players in the aggravation of HIV 1 pathogenesis, and as an unsuspected target to develop novel therapeutics against AIDS/TB co morbidity.