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Visualizing Non-lytic Exocytosis of Cryptococcus neoformans from Macrophages Using Digital Light Microscopy
10:02

Visualizing Non-lytic Exocytosis of Cryptococcus neoformans from Macrophages Using Digital Light Microscopy

Published on: October 21, 2014

Cryptococcus neoformans variants generated by phenotypic switching differ in virulence through effects on macrophage

A Guerrero1, N Jain, X Wang

  • 1Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.

Infection and Immunity
|January 6, 2010
PubMed

Insights

Macrophages drive cryptococcosis pathogenesis. This study reveals distinct macrophage interactions with Cryptococcus neoformans variants, highlighting their role in lung inflammation and damage during infection.

Area of Science:

  • Immunology
  • Microbiology
  • Pathogenesis

Background:

  • Macrophages are crucial in cryptococcosis, acting as defense cells, fungal reservoirs, and contributors to tissue damage.
  • Cryptococcus neoformans exhibits phenotypic switching, leading to different colony variants (e.g., smooth-colony (SM) and mucoid-colony (MC)) that may elicit distinct host responses.

Purpose of the Study:

  • To investigate the differential interactions between macrophages and SM versus MC variants of Cryptococcus neoformans.
  • To elucidate the role of macrophage activation and immune cell profiles in the pathogenesis of cryptococcosis caused by different fungal variants.

Main Methods:

  • Isolation and infection of alveolar macrophages (AMs) from mice with SM and MC variants of Cryptococcus neoformans.
  • Analysis of gene and surface expression of PD-L1, PD-L2, and major histocompatibility class II (MHC-II) on AMs.
  • Flow cytometry and cytokine analysis to assess macrophage activation, Th17 cell emergence, and interleukin-17 (IL-17) levels.

Main Results:

  • Alveolar macrophages from SM- and MC-infected mice showed differential expression of PD-L1, PD-L2, and MHC-II.
  • Macrophage activation in both SM- and MC-infected mice was characterized as alternatively activated.
  • MC infection led to the emergence of Th17 cells and elevated IL-17 levels in lung tissue, which were mitigated by AM depletion.

Conclusions:

  • Macrophages play a significant role in promoting inflammation and tissue damage in the lung during mucoid-colony variant Cryptococcus neoformans infection.
  • The distinct interactions of macrophages with different Cryptococcus neoformans variants influence the host immune response and disease outcome.

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