SCAN:Immune evasion through modulation of Rab and Arf small GTPases expression

ITQB Scan Seminar

Title: Immune evasion through modulation of Rab and Arf small GTPases expression

Speaker: Duarte C. Barral

Affiliation: Group Leader, Membrane Traffic in Infection and Disease, CEDOC- FCM/UNL

Abstract:

The uptake of microorganisms by phagocytosis involves the formation of a phagosome that matures by fusing with endocytic compartments, which results in the elimination of the enclosed microbe. However, intracellular pathogens can subvert this process by interfering with the function of different proteins, including small GTPases of the Rab and Arf families, which are master regulators of vesicular trafficking in the endocytic pathway. We found that the expression of Rab proteins is differentially modulated by bacteria and protozoa. When Rab14, whose expression is increased by the malaria parasite Plasmodium berghei, was silenced, we observed a significant increase in the phagocytosis of this parasite. Similarly, when Rab9a, whose expression is increased by Escherichia coli and Salmonella enterica, was silenced, we observed an increase in the phagocytosis of both bacterial species. Notably, the overexpression of these two Rab proteins caused the opposite effect. Thus, our studies suggest that the modulation of Rab expression by microbes is necessary for the success of the infection. We are currently characterizing the mechanisms by which the increased expression of Rab9a and Rab14 can lead to a decrease in phagocytosis. Furthermore, we are extending our analysis of the role of small GTPases in infection to Arf-like (Arl) proteins of the Arf family.