Bruton's Tyrosine Kinase (BTK) and Vav1 Contribute to Dectin1-Dependent Phagocytosis of Candida albicans in Macrophages

Karin Strijbis, Fikadu Tafesse, Gregory D. Fairn, Martin D. Witte, Stephanie K. Dougan, Nicki Watson, Eric Spooner, Alexandre Esteban, Valmik K. Vyas, Gerald R. Fink, Sergio Grinstein, Hidde L. Ploegh

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Phagocytosis of the opportunistic fungal pathogen Candida albicans by cells of the innate immune system is vital to prevent infection. Dectin-1 is the major phagocytic receptor involved in anti-fungal immunity. We identify two new interacting proteins of Dectin-1 in macrophages, Bruton's Tyrosine Kinase (BTK) and Vav1. BTK and Vav1 are recruited to phagocytic cups containing C. albicans yeasts or hyphae but are absent from mature phagosomes. BTK and Vav1 localize to cuff regions surrounding the hyphae, while Dectin-1 lines the full length of the phagosome. BTK and Vav1 colocalize with the lipid PI(3,4,5)P3 and F-actin at the phagocytic cup, but not with diacylglycerol (DAG) which marks more mature phagosomal membranes. Using a selective BTK inhibitor, we show that BTK contributes to DAG synthesis at the phagocytic cup and the subsequent recruitment of PKCε. BTK- or Vav1-deficient peritoneal macrophages display a defect in both zymosan and C. albicans phagocytosis. Bone marrow-derived macrophages that lack BTK or Vav1 show reduced uptake of C. albicans, comparable to Dectin1-deficient cells. BTK- or Vav1-deficient mice are more susceptible to systemic C. albicans infection than wild type mice. This work identifies an important role for BTK and Vav1 in immune responses against C. albicans.

Original languageEnglish (US)
Article numbere1003446
JournalPLoS Pathogens
Volume9
Issue number6
DOIs
StatePublished - Jun 2013
Externally publishedYes

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Candida albicans
Phagocytosis
Macrophages
Phagosomes
Hyphae
Diglycerides
Agammaglobulinaemia tyrosine kinase
Zymosan
Peritoneal Macrophages
Actins
Immune System
Immunity
Yeasts
Lipids
Membranes
Infection

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Bruton's Tyrosine Kinase (BTK) and Vav1 Contribute to Dectin1-Dependent Phagocytosis of Candida albicans in Macrophages. / Strijbis, Karin; Tafesse, Fikadu; Fairn, Gregory D.; Witte, Martin D.; Dougan, Stephanie K.; Watson, Nicki; Spooner, Eric; Esteban, Alexandre; Vyas, Valmik K.; Fink, Gerald R.; Grinstein, Sergio; Ploegh, Hidde L.

In: PLoS Pathogens, Vol. 9, No. 6, e1003446, 06.2013.

Research output: Contribution to journalArticle

Strijbis, K, Tafesse, F, Fairn, GD, Witte, MD, Dougan, SK, Watson, N, Spooner, E, Esteban, A, Vyas, VK, Fink, GR, Grinstein, S & Ploegh, HL 2013, 'Bruton's Tyrosine Kinase (BTK) and Vav1 Contribute to Dectin1-Dependent Phagocytosis of Candida albicans in Macrophages', PLoS Pathogens, vol. 9, no. 6, e1003446. https://doi.org/10.1371/journal.ppat.1003446
Strijbis, Karin ; Tafesse, Fikadu ; Fairn, Gregory D. ; Witte, Martin D. ; Dougan, Stephanie K. ; Watson, Nicki ; Spooner, Eric ; Esteban, Alexandre ; Vyas, Valmik K. ; Fink, Gerald R. ; Grinstein, Sergio ; Ploegh, Hidde L. / Bruton's Tyrosine Kinase (BTK) and Vav1 Contribute to Dectin1-Dependent Phagocytosis of Candida albicans in Macrophages. In: PLoS Pathogens. 2013 ; Vol. 9, No. 6.
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