TY - JOUR
T1 - Malaria parasite tyrosyl-tRNA synthetase secretion triggers pro-inflammatory responses
AU - Sharma, Amit
AU - Bhatt, Tarun Kumar
AU - Khan, Sameena
AU - Dwivedi, Ved Prakash
AU - Banday, Mudassir Meraj
AU - Sharma, Arvind
AU - Chandele, Anmol
AU - Camacho, Noelia
AU - De Pouplana, Llua S.Ribas
AU - Wu, Yang
AU - Craig, Alister G.
AU - Mikkonen, Antti Tapani
AU - Maier, Alexander Gerd
AU - Yogavel, Manickam
PY - 2011
Y1 - 2011
N2 - Malaria infection triggers pro-inflammatory responses in humans that are detrimental to host health. Parasite-induced enhancement in cytokine levels correlate with malaria-associated pathologies. Here we show that parasite tyrosyl-tRNA synthetase (PfTyrRS), a housekeeping protein translation enzyme, induces pro-inflammatory responses from host immune cells. PfTyrRS exits from the parasite cytoplasm into the infected red blood cell (iRBC) cytoplasm, from where it is released into the extracellular medium on iRBC lysis. Using its ELR peptide motif, PfTyrRS specifically binds to and internalizes into host macrophages, leading to enhanced secretion of the pro-inflammatory cytokines TNF-α ± and IL-6. PfTyrRS-macrophage interaction also augments expression of adherence-linked host endothelial receptors ICAM-1 and VCAM-1. Our description of PfTyrRS as a parasite-secreted protein that triggers pro-inflammatory host responses, along with its atomic resolution crystal structure in complex with tyrosyl-adenylate, provides a novel platform for targeting PfTyrRS in anti-parasitic strategies.
AB - Malaria infection triggers pro-inflammatory responses in humans that are detrimental to host health. Parasite-induced enhancement in cytokine levels correlate with malaria-associated pathologies. Here we show that parasite tyrosyl-tRNA synthetase (PfTyrRS), a housekeeping protein translation enzyme, induces pro-inflammatory responses from host immune cells. PfTyrRS exits from the parasite cytoplasm into the infected red blood cell (iRBC) cytoplasm, from where it is released into the extracellular medium on iRBC lysis. Using its ELR peptide motif, PfTyrRS specifically binds to and internalizes into host macrophages, leading to enhanced secretion of the pro-inflammatory cytokines TNF-α ± and IL-6. PfTyrRS-macrophage interaction also augments expression of adherence-linked host endothelial receptors ICAM-1 and VCAM-1. Our description of PfTyrRS as a parasite-secreted protein that triggers pro-inflammatory host responses, along with its atomic resolution crystal structure in complex with tyrosyl-adenylate, provides a novel platform for targeting PfTyrRS in anti-parasitic strategies.
UR - http://www.scopus.com/inward/record.url?scp=82555196544&partnerID=8YFLogxK
U2 - 10.1038/ncomms1522
DO - 10.1038/ncomms1522
M3 - Article
SN - 2041-1723
VL - 2
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 530
ER -