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

Theodore J. Kottom, Deanne M. Hebrink, Eva M. Carmona, Andrew H. Limper

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Pneumocystis major surface glycoprotein (Msg) is a 120-kD surface protein complex on the organism with importance in adhesion and immune recognition. In this study, we show that Msg significantly impairs tumor necrosis factor (TNF)-α secretion by macrophages induced by Saccharomyces cerevisiae and Pneumocystis carinii (Pc) β-glucans. METHODS: Major surface glycoprotein was shown to greatly reduce β-glucan-induced Dectin-1 immunoreceptor tyrosine-based activating motif (ITAM) phosphorylation. Major surface glycoprotein also down regulated Dectin-1 receptor messenger ribonucleic acid (mRNA) expression in the macrophages. It is interesting that Msg incubation with macrophages resulted in significant mRNA upregulation of both C-type lectin receptors (CLR) Mincle and MCL in Msg protein presence alone but to even greater amounts in the presence of Pc β-glucan. RESULTS: The silencing of MCL and Mincle resulted in TNF-α secretions similar to that of macrophages treated with Pneumocystis β-glucan alone, which is suggestive of an inhibitory role for these 2 CLRs in Msg-suppressive effects on host cell immune response. CONCLUSIONS: Taken together, these data indicate that the Pneumocystis Msg surface protein complex can act to suppress host macrophage inflammatory responses to the proinflammatory β -glucan components of the organisms.

Original languageEnglish (US)
Pages (from-to)1213-1221
Number of pages9
JournalThe Journal of infectious diseases
Volume222
Issue number7
DOIs
StatePublished - Sep 1 2020

Keywords

  • Pneumocystis
  • Msg
  • major surface glycoprotein
  • MCL
  • Mincle

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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