Immune cells fold and damage fungal hyphae

Proc Natl Acad Sci U S A. 2021 Apr 13;118(15):e2020484118. doi: 10.1073/pnas.2020484118.

Abstract

Innate immunity provides essential protection against life-threatening fungal infections. However, the outcomes of individual skirmishes between immune cells and fungal pathogens are not a foregone conclusion because some pathogens have evolved mechanisms to evade phagocytic recognition, engulfment, and killing. For example, Candida albicans can escape phagocytosis by activating cellular morphogenesis to form lengthy hyphae that are challenging to engulf. Through live imaging of C. albicans-macrophage interactions, we discovered that macrophages can counteract this by folding fungal hyphae. The folding of fungal hyphae is promoted by Dectin-1, β2-integrin, VASP, actin-myosin polymerization, and cell motility. Folding facilitates the complete engulfment of long hyphae in some cases and it inhibits hyphal growth, presumably tipping the balance toward successful fungal clearance.

Keywords: cytoskeleton; fungal hyphae; macrophages; mechanical force; podosomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • Actomyosin / metabolism
  • Animals
  • CD18 Antigens / metabolism
  • Candida albicans / pathogenicity*
  • Cell Adhesion Molecules / metabolism
  • Cells, Cultured
  • Humans
  • Hyphae / cytology*
  • Hyphae / pathogenicity
  • Lectins, C-Type / metabolism
  • Macrophages / metabolism*
  • Macrophages / microbiology
  • Mice
  • Phagocytosis*
  • Protein Kinases / metabolism
  • RAW 264.7 Cells

Substances

  • CD18 Antigens
  • Cell Adhesion Molecules
  • Lectins, C-Type
  • dectin 1
  • Actomyosin
  • Protein Kinases
  • AMP-Activated Protein Kinase Kinases