Interleukin 1α is critical for resistance against highly virulent Aspergillus fumigatus isolates Journal Article
| Authors: | Caffrey-Carr, A. K.; Kowalski, C. H.; Beattie, S. R.; Blaseg, N. A.; Upshaw, C. R.; Thammahong, A.; Lust, H. E.; Tang, Y. W.; Hohl, T. M.; Cramer, R. A.; Obar, J. J. |
| Article Title: | Interleukin 1α is critical for resistance against highly virulent Aspergillus fumigatus isolates |
| Abstract: | Heterogeneity among Aspergillus fumigatus isolates results in unique virulence potential and inflammatory responses. How these isolates drive specific immune responses and how this affects fungally induced lung damage and disease outcome are unresolved. We demonstrate that the highly virulent CEA10 strain is able to rapidly germinate within the immunocompetent lung environment, inducing greater lung damage, vascular leakage, and interleukin 1α (IL-1α) release than the low-virulence Af293 strain, which germinates with a lower frequency in this environment. Importantly, the clearance of CEA10 was consequently dependent on IL-1α, in contrast to Af293. The release of IL-1α occurred by a caspase 1/11- and P2XR7-independent mechanism but was dependent on calpain activity. Our finding that early fungal conidium germination drives greater lung damage and IL-1α-dependent inflammation is supported by three independent experimental lines. First, pregermination of Af293 prior to in vivo challenge drives greater lung damage and an IL-1α-dependent neutrophil response. Second, the more virulent EVOL20 strain, derived from Af293, is able to germinate in the airways, leading to enhanced lung damage and IL-1α- dependent inflammation and fungal clearance. Third, primary environmental A. fumigatus isolates that rapidly germinate under airway conditions follow the same trend toward IL-1α dependency. Our data support the hypothesis that A. fumigatus phenotypic variation significantly contributes to disease outcomes. © 2017 American Society for Microbiology. |
| Keywords: | controlled study; nonhuman; animal cell; mouse; animal experiment; animal model; inflammation; in vivo study; enzyme activity; neutrophil; innate immunity; neutrophils; cytokine release; lung infection; interleukin 1alpha; aspergillus fumigatus; conidium; fungal spore germination; aspergillosis; interleukin 1beta converting enzyme; fungal strain; lung injury; infection resistance; invasive fungal infection; fungal virulence; mucosal immunity; fungus immunity; calpain; priority journal; article; caspase 11; il-1; lung defense; respiratory pathogens; purinergic p2x7 receptor; pathogen clearance |
| Journal Title: | Infection and Immunity |
| Volume: | 85 |
| Issue: | 12 |
| ISSN: | 0019-9567 |
| Publisher: | American Society for Microbiology |
| Date Published: | 2017-12-01 |
| Start Page: | e00661-17 |
| Language: | English |
| DOI: | 10.1128/iai.00661-17 |
| PROVIDER: | scopus |
| PMCID: | PMC5695118 |
| PUBMED: | 28947643 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 January 2018 -- Source: Scopus |
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