TY - JOUR T1 - Leishmania survives by exporting miR-146a from infected to resident cells to subjugate inflammation JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202101229 VL - 5 IS - 6 SP - e202101229 AU - Satarupa Ganguly AU - Bartika Ghoshal AU - Ishani Banerji AU - Shreya Bhattacharjee AU - Sreemoyee Chakraborty AU - Avijit Goswami AU - Kamalika Mukherjee AU - Suvendra N Bhattacharyya Y1 - 2022/06/01 UR - https://www.life-science-alliance.org/content/5/6/e202101229.abstract N2 - Leishmania donovani, the causative agent of visceral leishmaniasis, infects and resides within tissue macrophage cells. It is not clear how the parasite infected cells crosstalk with the noninfected cells to regulate the infection process. During infection, Leishmania adopts a dual strategy for its survival by regulating the intercellular transport of host miRNAs to restrict inflammation. The parasite, by preventing mitochondrial function of host cells, restricts the entry of liver cell derived miR-122–containing extracellular vesicles in infected macrophages to curtail the inflammatory response associated with miR-122 entry. On contrary, the parasite up-regulates the export of miR-146a from the infected macrophages. The miR-146a, associated with the extracellular vesicles released by infected cells, restricts miR-122 production in hepatocytes while polarizing neighbouring naïve macrophages to the M2 state by affecting the cytokine expression. On entering the recipient macrophages, miR-146a dominates the miRNA antagonist RNA-binding protein HuR to inhibit the expression of proinflammatory cytokine mRNAs having HuR-interacting AU-rich elements whereas up-regulates anti-inflammatory IL-10 by exporting the miR-21 to polarize the recipient cells to M2 stage. ER -