Cryptococcus neoformans Induces MCP-1 Release and Delays the Death of Human Mast Cells

Front Cell Infect Microbiol. 2019 Aug 13:9:289. doi: 10.3389/fcimb.2019.00289. eCollection 2019.

Abstract

Cryptococcosis, caused by the basidiomycete Cryptococcus neoformans, is a life-threatening disease affecting approximately one million people per year worldwide. Infection can occur when C. neoformans cells are inhaled by immunocompromised people. In order to establish infection, the yeast must bypass recognition and clearance by immune cells guarding the tissue. Using in vitro infections, we characterized the role of mast cells (MCs) in cryptococcosis. We found that MCs recognize C. neoformans and release inflammatory mediators such as tryptase and cytokines. From the latter group MCs released mainly CCL-2/MCP-1, a strong chemoattractant for monocytic cells. We demonstrated that supernatants of infected MCs recruit monocytes but not neutrophils. During infection with C. neoformans, MCs have a limited ability to kill the yeast depending on the serotype. C. neoformans, in turn, modulates the lifespan of MCs both, by presence of its polysaccharide capsule and by secreting soluble modulators. Taken together, MCs might have important contributions to fungal clearance during early stages of cryptocococis where these cells regulate recruitment of monocytes to mucosal tissues.

Keywords: Cryptococcus neoformans; fungi; innate immunity; mast cells; monocyte chemoattractant protein 1/CCL-2; monocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Death
  • Cell Degranulation / immunology
  • Chemokine CCL2 / biosynthesis*
  • Chemotaxis, Leukocyte / immunology
  • Cryptococcosis / immunology
  • Cryptococcosis / metabolism*
  • Cryptococcosis / microbiology*
  • Cryptococcus neoformans / physiology*
  • Cytokines / metabolism
  • Host-Pathogen Interactions*
  • Humans
  • Mast Cells / immunology
  • Mast Cells / metabolism*
  • Mast Cells / microbiology*
  • Monocytes / immunology
  • Monocytes / metabolism
  • Monocytes / microbiology
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Phagocytosis

Substances

  • CCL2 protein, human
  • Chemokine CCL2
  • Cytokines