The trophic life cycle stage of the opportunistic fungal pathogen Pneumocystis murina hinders the ability of dendritic cells to stimulate CD4+ T cell responses

Heather M. Evans, Andrew Simpson, Shu Shen, Arnold J. Stromberg, Carol L. Pickett, Beth A. Garvy

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The life cycle of the opportunistic fungal pathogen Pneumocystis murina consists of a trophic stage and an ascus-like cystic stage. Infection with the cyst stage induces proinflammatory immune responses, while trophic forms suppress the cytokine response to multiple pathogen-associated molecular patterns (PAMPs), including β-glucan. A targeted gene expression assay was used to evaluate the dendritic cell response following stimulation with trophic forms alone, with a normal mixture of trophic forms and cysts, or with β-glucan. We demonstrate that stimulation with trophic forms downregulated the expression of multiple genes normally associated with the response to infection, including genes encoding transcription factors. Trophic forms also suppressed the expression of genes related to antigen processing and presentation, including the gene encoding the major histocompatibility complex (MHC) class II transactivator, CIITA. Stimulation of dendritic cells with trophic forms, but not a mixture of trophic forms and cysts, reduced the expression of MHC class II and the costimulatory molecule CD40 on the surface of the cells. These defects in the expression of MHC class II and costimulatory molecules corresponded with a reduced capacity for trophic form-loaded dendritic cells to stimulate CD4+ T cell proliferation and polarization. These data are consistent with the delayed innate and adaptive responses previously observed in immunocompetent mice inoculated with trophic forms compared to responses in mice inoculated with a mixture of trophic forms and cysts. We propose that trophic forms broadly inhibit the ability of dendritic cells to fulfill their role as antigen-presenting cells.

Original languageEnglish
Article numbere00396-17
JournalInfection and Immunity
Volume85
Issue number10
DOIs
StatePublished - 2017

Bibliographical note

Publisher Copyright:
© 2017 American Society for Microbiology.

Keywords

  • Cytokines
  • Dendritic cells
  • Fungal infection
  • Lung defense
  • Pneumocystis
  • T cells

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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