Pneumocystis carinii Major Surface Glycoprotein Dampens Macrophage Inflammatory Responses to Fungal β-Glucan

Theodore J Kottom1, Deanne M Hebrink1, Eva M Carmona1

  • 1Thoracic Diseases Research Unit, Departments of Medicine and Biochemistry, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.

Abstract

Insights

Pneumocystis major surface glycoprotein (Msg) suppresses macrophage inflammatory responses. Msg inhibits tumor necrosis factor-alpha secretion by impairing Dectin-1 signaling and upregulating other C-type lectin receptors.

Area of Science:

  • Immunology
  • Microbiology
  • Molecular Biology

Background:

  • Pneumocystis major surface glycoprotein (Msg) is a 120-kD complex crucial for Pneumocystis adhesion and immune recognition.
  • Msg plays a role in modulating host immune responses to Pneumocystis infections.

Purpose of the Study:

  • To investigate the effect of Pneumocystis major surface glycoprotein (Msg) on macrophage inflammatory responses.
  • To elucidate the mechanisms by which Msg influences cytokine secretion and receptor expression.

Main Methods:

  • Assessed tumor necrosis factor-alpha (TNF-α) secretion by macrophages stimulated with Saccharomyces cerevisiae and Pneumocystis carinii (Pc) β-glucans in the presence of Msg.
  • Analyzed Dectin-1 immunoreceptor tyrosine-based activating motif (ITAM) phosphorylation and Dectin-1 receptor mRNA expression.
  • Investigated the expression of C-type lectin receptors (CLRs) Mincle and MCL upon Msg incubation with macrophages.

Main Results:

  • Msg significantly impaired TNF-α secretion induced by β-glucans.
  • Msg reduced Dectin-1 ITAM phosphorylation and mRNA expression.
  • Msg upregulated Mincle and MCL mRNA expression, particularly in the presence of Pc β-glucan.

Conclusions:

  • Pneumocystis Msg suppresses host macrophage inflammatory responses to β-glucan components.
  • Mincle and MCL appear to play an inhibitory role in Msg-mediated suppression of host immune responses.