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Malaria parasite tyrosyl-tRNA synthetase secretion triggers pro-inflammatory responses.

Bhatt, Tarun Kumar, Khan, Sameena, Dwivedi, Ved Prakash, Banday, Mudassir Meraj, Sharma, Arvind, Chandele, Anmol, Camacho, Noelia, de Pouplana, Lluís Ribas, Wu, Yang, Craig, Alister ORCID: https://orcid.org/0000-0003-0914-6164, Mikkonen, Antti Tapani, Maier, Alexander Gerd, Yogavel, Manickam and Sharma, Amit (2011) 'Malaria parasite tyrosyl-tRNA synthetase secretion triggers pro-inflammatory responses.'. Nature communications, Vol 2, p. 530.

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Abstract

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.

Item Type: Article
Subjects: QU Biochemistry > Cells and Genetics > QU 375 Cell physiology
QW Microbiology and Immunology > Reference Works. General Immunology > QW 520 Research (General)
QX Parasitology > QX 20 Research (General)
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department: Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI): https://doi.org/10.1038/ncomms1522
Depositing User: Mary Creegan
Date Deposited: 14 Nov 2011 15:28
Last Modified: 17 Jul 2019 14:14
URI: https://archive.lstmed.ac.uk/id/eprint/2435

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