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© Research
Publication : PLoS pathogens

A polysaccharide virulence factor from Aspergillus fumigatus elicits anti-inflammatory effects through induction of Interleukin-1 receptor antagonist

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in PLoS pathogens - 06 Mar 2014

Gresnigt MS, Bozza S, Becker KL, Joosten LA, Abdollahi-Roodsaz S, van der Berg WB, Dinarello CA, Netea MG, Fontaine T, De Luca A, Moretti S, Romani L, Latge JP, van de Veerdonk FL

Link to Pubmed [PMID] – 24603878

PLoS Pathog. 2014 Mar;10(3):e1003936

The galactosaminogalactan (GAG) is a cell wall component of Aspergillus fumigatus that has potent anti-inflammatory effects in mice. However, the mechanisms responsible for the anti-inflammatory property of GAG remain to be elucidated. In the present study we used in vitro PBMC stimulation assays to demonstrate, that GAG inhibits proinflammatory T-helper (Th)1 and Th17 cytokine production in human PBMCs by inducing Interleukin-1 receptor antagonist (IL-1Ra), a potent anti-inflammatory cytokine that blocks IL-1 signalling. GAG cannot suppress human T-helper cytokine production in the presence of neutralizing antibodies against IL-1Ra. In a mouse model of invasive aspergillosis, GAG induces IL-1Ra in vivo, and the increased susceptibility to invasive aspergillosis in the presence of GAG in wild type mice is not observed in mice deficient for IL-1Ra. Additionally, we demonstrate that the capacity of GAG to induce IL-1Ra could also be used for treatment of inflammatory diseases, as GAG was able to reduce severity of an experimental model of allergic aspergillosis, and in a murine DSS-induced colitis model. In the setting of invasive aspergillosis, GAG has a significant immunomodulatory function by inducing IL-1Ra and notably IL-1Ra knockout mice are completely protected to invasive pulmonary aspergillosis. This opens new treatment strategies that target IL-1Ra in the setting of acute invasive fungal infection. However, the observation that GAG can also protect mice from allergy and colitis makes GAG or a derivative structure of GAG a potential treatment compound for IL-1 driven inflammatory diseases.

http://www.ncbi.nlm.nih.gov/pubmed/24603878