Stage-specific innate immune recognition of Aspergillus fumigatus and modulation by echinocandrin drugs Journal Article


Author: Hohl, T. M.
Article Title: Stage-specific innate immune recognition of Aspergillus fumigatus and modulation by echinocandrin drugs
Abstract: The pulmonary innate immune system clears inhaled Aspergillus fumigatus conidia (spores) from terminal airways. Failure to control conidial germination in immune compromised hosts can result in hyphal tissue invasion and fatal disease. Insight into the molecular recognition of A. fumigatus by host leukocytes indicates that the innate immune system exploits obligate changes in fungal cell wall composition that occur at the first stage of germination, conidial swelling. Germinating spores activate at least two host signal transduction pathways. Surface exposure of fungal β-(1,3) glucan, a polysaccharide constituent of the fungal cell wall, triggers dectin-1 signaling by host phagocytes. Spore germination leads to the induction of Toll-like receptor (TLR) signaling as well. This stage-specific recognition mechanism focuses host antifungal responses on cells with the potential for tissue invasion and may serve to limit potentially deleterious effects of inflammation in space and time. Fungal β-(1,3) glucan not only activates host innate immune responses but also represents the target of echinocandin drugs. The activity of echinocandin drugs has largely been understood on the basis of pharmacologic growth inhibition of yeast and moulds, resulting in lysis of yeast cells and stunting of dysmorphic hyphae. The recognition that fungal β-1,3 glucan activates dectin-1 signaling suggests that echinocandin drugs may exert immune modulatory effects by altering innate immune responses to drug-treated fungal cells, a view supported by recent data from studies on C. albicans, A. fumigatus, and non-Aspergillus moulds.
Keywords: signal transduction; nonhuman; protein function; inflammation; toll like receptor 4; cell wall; tumor necrosis factor alpha; neutrophil; antigen recognition; cytokine production; innate immunity; immunomodulation; host resistance; macrophage; cxcl2 chemokine; caspofungin; aspergillus; dectin; echinocandin; fungus; toll-like receptor; 1,3 beta glucan synthase; beta 1,3 glucan; dectin 1; myeloid differentiation factor 88; toll like receptor; toll like receptor 2; aspergillus fumigatus; candida albicans; conidium; fungal spore germination; fungus hyphae; fungi
Journal Title: Medical Mycology
Volume: 47
Issue: Suppl. 1
ISSN: 1369-3786
Publisher: Oxford University Press  
Date Published: 2009-01-01
Start Page: S192
End Page: S198
Language: English
DOI: 10.1080/13693780802078131
PROVIDER: scopus
PMCID: PMC3808522
PUBMED: 18608931
DOI/URL:
Notes: --- - "Export Date: 30 November 2010" - "CODEN: MEMYF" - "Source: Scopus"
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. Tobias Martin Hohl
    105 Hohl