Merocytophagy contributes to dissemination of Francisella tularensis and is enhanced by SYK signaling in macrophages

Abstract

Abstract Merocytophagy is a phagocytic process characterized by the transfer of cytosolic content between macrophages and the formation of a double-membraned vesical within recipient cells. Studies conducted in our laboratory have demonstrated that proteins and intracellular pathogens can be transferred between cells by this contact-dependent mechanism. In particular, Francisella tularensis, a highly infectious pathogen that spreads from cell to cell by hijacking the phagocytic pathway in macrophages, has been shown to replicate within cells that receive cargo via merocytophagy. While these observations may point to an alternative route of F. tularensis dissemination in vivo, it is also possible that this mechanism of bacterial spread could amplify immune responses. Ongoing studies aim to characterize molecular and cellular players in merocytophagy to gain a better understanding of this phenomenon and to develop strategies to assess merocytophagy in vivo in the future. In cell-to-cell contact studies, inhibition of spleen tyrosine kinase (SYK) expression and activity showed decreased cargo transfer by merocytophagy. Pharmacologic inhibition of SYK was also associated with decreased surface expression of several integrins, giving evidence that cell-to-cell contact is stabilized by integrins during merocytophagic transfer in macrophages. Supported by grants from NIH and NIGMS (R56 AI139476 and T32 GM008336).