Cytosolic Access of : Critical Impact of Phagosomal Acidification Control and Demonstration of Occurrence

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The intracellular fate of the agent of the human tuberculosis agent in phagocytes is a question of great biological relevance. Among the mycobacterial survival strategies, the escape of Mycobacterium tuberculosis from phagosomes has been subject of scientific debate for a long time. However, technically improved methods recently reinforced the occurrence of this phenomenon. Here, we focused on the host factors involved in phagosomal rupture and provide first and singular evidence of M. tuberculosis-mediated phagosomal rupture in vivo in mouse lungs and inside the granuloma. We show that partial blockage of phagosomal acidification, induced by mycobacteria, is a prerequisite for efficient vacuolar breakage by M. tuberculosis and link maturation arrest, cytosolic contact and the corresponding immune responses. From our results we conclude that vacuolar breakage induced by M. tuberculosis is not an ex vivo artifact of cell cultures, but an important process that occurs inside infected phagocytes within organs during several days that strongly determines the outcome of infection with this key pathogen.

Vyšlo v časopise: Cytosolic Access of : Critical Impact of Phagosomal Acidification Control and Demonstration of Occurrence. PLoS Pathog 11(2): e32767. doi:10.1371/journal.ppat.1004650
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004650

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