RT Journal Article
SR Electronic
T1 Leishmania survives by exporting miR-146a from infected to resident cells to subjugate inflammation
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202101229
DO 10.26508/lsa.202101229
VO 5
IS 6
A1 Satarupa Ganguly
A1 Bartika Ghoshal
A1 Ishani Banerji
A1 Shreya Bhattacharjee
A1 Sreemoyee Chakraborty
A1 Avijit Goswami
A1 Kamalika Mukherjee
A1 Suvendra N Bhattacharyya
YR 2022
UL https://www.life-science-alliance.org/content/5/6/e202101229.abstract
AB 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.