The Abl and Arg Kinases Mediate Distinct Modes of Phagocytosis and Are Required for Maximal Leishmania Infection

Dawn M. Wetzel, Diane McMahon-Pratt, Anthony J. Koleske

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Leishmania, an obligate intracellular parasite, binds several receptors to trigger engulfment by phagocytes, leading to cutaneous or visceral disease. These receptors include complement receptor 3 (CR3), used by promastigotes, and the Fc receptor (FcR), used by amastigotes. The mechanisms mediating uptake are not well understood. Here we show that Abl family kinases mediate both phagocytosis and the uptake of Leishmania amazonensis by macrophages (MF{cyrillic}s). Imatinib, an Abl/Arg kinase inhibitor, decreases opsonized polystyrene bead phagocytosis and Leishmania uptake. Interestingly, phagocytosis of IgG-coated beads is decreased in Arg-deficientMF{cyrillic}s, while that of C3bi-coated beads is unaffected. Conversely, uptake of C3bi-coated beads is decreased in Abl-deficientMF{cyrillic}s, but that of IgG-coated beads is unaffected. Consistent with these results, Abl-deficientMF{cyrillic}s are inefficient at C3bi-opsonized promastigote uptake, and Arg-deficientMF{cyrillic}s are defective in IgG1-opsonized amastigote uptake. Finally, genetic loss of Abl or Arg reduces infection severity in murine cutaneous leishmaniasis, and imatinib treatment results in smaller lesions with fewer parasites than in controls. Our studies are the first to demonstrate that efficient phagocytosis and maximal Leishmania infection require Abl family kinases. These results highlight Abl family kinase-mediated signaling pathways as potential therapeutic targets for leishmaniasis.

Original languageEnglish (US)
Pages (from-to)3176-3186
Number of pages11
JournalMolecular and Cellular Biology
Volume32
Issue number15
DOIs
StatePublished - Aug 2012

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Leishmania
Complement C3b
Phagocytosis
Phosphotransferases
Immunoglobulin G
Infection
Macrophage-1 Antigen
Communicable Disease Control
Cutaneous Leishmaniasis
Leishmaniasis
Fc Receptors
Polystyrenes
Phagocytes
Parasites
Macrophages
Skin
Imatinib Mesylate
Therapeutics

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

The Abl and Arg Kinases Mediate Distinct Modes of Phagocytosis and Are Required for Maximal Leishmania Infection. / Wetzel, Dawn M.; McMahon-Pratt, Diane; Koleske, Anthony J.

In: Molecular and Cellular Biology, Vol. 32, No. 15, 08.2012, p. 3176-3186.

Research output: Contribution to journalArticle

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