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Exogenous pentraxin 3 restores antifungal resistance and restrains inflammation in murine chronic granulomatous disease
- Source :
- Journal of immunology (Baltimore, Md. : 1950). 183(7)
- Publication Year :
- 2009
-
Abstract
- Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by life-threatening bacterial and fungal infections and hyperinflammation. The susceptibility to aspergillosis in experimental CGD (p47phox−/− mice) is associated with the failure to control the inherent inflammatory response to the fungus and to restrict the activation of inflammatory Th17 cells. We assessed whether pentraxin (PTX)3, a member of a family of multimeric pattern-recognition proteins with potent anti-Aspergillus activity, could limit pathogenic inflammation in p47phox−/− mice by curbing the IL–23/Th17 inflammatory axis in response to the fungus. We found that the production of PTX3 was delayed in CGD mice in infection but exogenous administration of PTX3 early in infection restored antifungal resistance and restrained the inflammatory response to the fungus. This occurred through down-regulation of IL-23 production by dendritic cells and epithelial cells which resulted in limited expansion of IL-23R+ γδ+ T cells producing IL-17A and the emergence of Th1/Treg responses with minimum pathology. Thus, PTX3 could be therapeutically used for the exploitation of NADPH-independent mechanism(s) of antifungal immune protection with limited immunopathology in CGD.
- Subjects :
- Antifungal Agents
Immunology
Inflammation
Drug resistance
CHO Cells
Biology
Aspergillosis
Granulomatous Disease, Chronic
Microbiology
Mice
Chronic granulomatous disease
Cricetulus
Drug Resistance, Fungal
hemic and lymphatic diseases
Immunopathology
Cricetinae
Gene Expression Regulation, Fungal
medicine
Immunology and Allergy
Animals
Cells, Cultured
Mice, Knockout
Aspergillus fumigatus
Fungal genetics
PTX3
medicine.disease
Mice, Inbred C57BL
Serum Amyloid P-Component
C-Reactive Protein
Primary immunodeficiency
Pulmonary Aspergillosis
medicine.symptom
Inflammation Mediators
Subjects
Details
- ISSN :
- 15506606
- Volume :
- 183
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Accession number :
- edsair.doi.dedup.....90010fd4397428c6de089626b1157a8a