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

Author

Listed:
  • Tarun Kumar Bhatt

    (Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB))

  • Sameena Khan

    (Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB))

  • Ved Prakash Dwivedi

    (Immunology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB))

  • Mudassir Meraj Banday

    (Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB))

  • Arvind Sharma

    (Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB))

  • Anmol Chandele

    (Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB))

  • Noelia Camacho

    (Institute for Research in Biomedicine (IRB), C/ Baldiri Reixac 15-21, 08028 Barcelona, Catalonia, Spain.)

  • Lluís Ribas de Pouplana

    (Catalan Institution for Research and Advanced Studies (ICREA), Passeig Lluís Companys 23, 08010 Barcelona, Catalonia, Spain.)

  • Yang Wu

    (Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.)

  • Alister G. Craig

    (Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.)

  • Antti Tapani Mikkonen

    (La Trobe Institute for Molecular Science, La Trobe University, Melbourne Victoria 3086, Australia.)

  • Alexander Gerd Maier

    (La Trobe Institute for Molecular Science, La Trobe University, Melbourne Victoria 3086, Australia.)

  • Manickam Yogavel

    (Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB))

  • Amit Sharma

    (Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB))

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.

Suggested Citation

  • Tarun Kumar Bhatt & Sameena Khan & Ved Prakash Dwivedi & Mudassir Meraj Banday & Arvind Sharma & Anmol Chandele & Noelia Camacho & Lluís Ribas de Pouplana & Yang Wu & Alister G. Craig & Antti Tapani M, 2011. "Malaria parasite tyrosyl-tRNA synthetase secretion triggers pro-inflammatory responses," Nature Communications, Nature, vol. 2(1), pages 1-11, September.
    • Handle: RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1522
    DOI: 10.1038/ncomms1522
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