Eosinophils utilize multiple chemokine receptors for chemotaxis to the parasitic nematode strongyloides stercoralis

Louis H. Stein, Kevin M. Redding, James J. Lee, Thomas J. Nolan, Gerhard A. Schad, James B. Lok, David Abraham

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Protective innate immunity to the nematode Strongyloides stercoralis requires eosinophils in the parasite killing process. Experiments were performed to determine if an extract of S. stercoralis would trigger eosinophil chemotaxis, and to then compare the chemotactic migration response, including second messenger signals and receptors, to those mechanisms triggered by host chemoattractants. Eosinophils undergo both chemotaxis and chemokinesis to soluble parasite extract in transwell plates. Pretreatment of eosinophils with pertussis toxin, a G protein-coupled receptor inhibitor, inhibited migration of the eosinophils to the parasite extract. Likewise, blocking PI3K, tyrosine kinase, p38 and p44/42 inhibited eosinophil chemotaxis to parasite extract. Furthermore, CCR3, CXCR4 or CXCR2 antagonists significantly inhibited eosinophil chemotaxis to the parasite extract. Molecular weight fractionation of parasite extract revealed that molecules attracting eosinophils were present in several fractions, with molecules greater than 30 kDa being the most potent. Treating the extract with proteinase K or chitinase significantly inhibited its ability to induce chemotaxis, thereby demonstrating that the chemoattractants were both protein and chitin. Therefore, chemoattractants derived from parasites and host species stimulate similar receptors and second messenger signals to induce eosinophil chemotaxis. Parasite extract stimulates multiple receptors on the eosinophil surface, which ensures a robust innate immune response to the parasite.

Original languageEnglish (US)
Pages (from-to)618-630
Number of pages13
JournalJournal of Innate Immunity
Volume1
Issue number6
DOIs
StatePublished - Oct 1 2009

Keywords

  • CCR3
  • CXCR2
  • CXCR4
  • Chemotaxis
  • Eosinophil
  • Strongyloides stercoralis

ASJC Scopus subject areas

  • Immunology and Allergy

Fingerprint Dive into the research topics of 'Eosinophils utilize multiple chemokine receptors for chemotaxis to the parasitic nematode strongyloides stercoralis'. Together they form a unique fingerprint.

  • Cite this

    Stein, L. H., Redding, K. M., Lee, J. J., Nolan, T. J., Schad, G. A., Lok, J. B., & Abraham, D. (2009). Eosinophils utilize multiple chemokine receptors for chemotaxis to the parasitic nematode strongyloides stercoralis. Journal of Innate Immunity, 1(6), 618-630. https://doi.org/10.1159/000233235