Tracing conidial fate and measuring host cell antifungal activity using a reporter of microbial viability in the lung. Academic Article uri icon

Overview

MeSH

  • Adaptor Proteins, Signal Transducing
  • Animals
  • CARD Signaling Adaptor Proteins
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Mice, Knockout
  • Protein-Tyrosine Kinases
  • Syk Kinase

MeSH Major

  • Aspergillosis
  • Aspergillus fumigatus
  • Host-Pathogen Interactions
  • Immunity, Innate
  • Lung
  • Pneumonia
  • Spores, Fungal

abstract

  • Fluorescence can be harnessed to monitor microbial fate and to investigate functional outcomes of individual microbial cell-host cell encounters at portals of entry in native tissue environments. We illustrate this concept by introducing fluorescent Aspergillus reporter (FLARE) conidia that simultaneously report phagocytic uptake and fungal viability during cellular interactions with the murine respiratory innate immune system. Our studies using FLARE conidia reveal stepwise and cell-type-specific requirements for CARD9 and Syk, transducers of C-type lectin receptor and integrin signals, in neutrophil recruitment, conidial uptake, and conidial killing in the lung. By achieving single-event resolution in defined leukocyte populations, the FLARE method enables host cell profiling on the basis of pathogen uptake and killing and may be extended to other pathogens in diverse model host organisms to query molecular, cellular, and pharmacologic mechanisms that shape host-microbe interactions. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

publication date

  • December 27, 2012

has subject area

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Aspergillosis
  • Aspergillus fumigatus
  • CARD Signaling Adaptor Proteins
  • Host-Pathogen Interactions
  • Immunity, Innate
  • Intracellular Signaling Peptides and Proteins
  • Lung
  • Mice
  • Mice, Knockout
  • Pneumonia
  • Protein-Tyrosine Kinases
  • Spores, Fungal
  • Syk Kinase

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3712646

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2012.10.026

PubMed ID

  • 23200858

Additional Document Info

start page

  • 1762

end page

  • 1773

volume

  • 2

number

  • 6