Malaria derived extracellular vesicles inhibit neutrophils ROS production and NETs formation

Abstract

IntroductionA dysfunctional innate immune response is believed to provide immune evasion of the malaria parasites, but also to cause increased susceptibility to bacterial infections. Neutrophils are the most abundant cells found in the blood circulation in direct contact with parasite infected red extracellular vesicles (EVs) derived from iRBCs, containing both parasite and host materials, including microRNAs, modulate neutrophil response by transferring regulatory microRNAs.Methods and ResultsWe have previously reported that malaria EVs contain miR451a, a microRNA that is known to regulate neutrophil activity when EVs are phagocytized by neutrophils. Thus we monitored the uptake of EVs by neutrophils by fluorescence microscopy, confocal microscopy and real‐time polymerase chain reaction techniques as well as potential pathways involved in their uptakes by neutrophils. Furthermore, our data demonstrated the influence of malaria induced EVs on human neutrophil functions in vitro by inhibiting their ability to produce ROS and suppressing cytokine secretion. Neutrophils are known to produce neutrophil extracellular traps (NETs) during immune response to pathogens; therefore, we quantified the production of NETs with incubation of EVs.ConclusionOur data indicate that EVs are actively taken up by neutrophils to deliver miR­451, thereby interfering with their capacity to kill bacteria by inhibiting ROS and NETs formation. We describe a new mechanism of cellular communication between parasites and the host immune system. While EVs might increase tolerance to the parasites, they dramatically affect the resistance to a co­infection by bacteria. The elucidation of the immune regulatory role of EVs might lead to the development of new therapies.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.