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dc.contributor.authorCaffrey-Carr, Alayna K.
dc.contributor.authorKowalski, Caitlin H.
dc.contributor.authorBeattie, Sarah R.
dc.contributor.authorBlaseg, Nathan A.
dc.contributor.authorUpshaw, Chanell R.
dc.contributor.authorThammahong, Arsa
dc.contributor.authorLust, Hannah E.
dc.contributor.authorTang, Yi-Wei
dc.contributor.authorHohl, Tobias M.
dc.contributor.authorCramer, Robert A.
dc.contributor.authorObar, Joshua J.
dc.identifier.citationCaffrey-Carr, Alayna K. , Caitlin H. Kowalski, Sarah R. Beattie, Nathan A. Blaseg, Chanell R. Upshaw, Arsa Thammahong, Hannah E. Lust, Yi-Wei Tang, Tobias M. Hohl, Robert A. Cramer, and Joshua J. Obar. "Interleukin 1α Is Critical for Resistance against Highly Virulent Aspergillus fumigatus Isolates" Infection & Immunity 85, no. 12 (September 2017). DOI: 10.1128/IAI.00661-17.en_US
dc.description.abstractHeterogeneity 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.en_US
dc.titleInterleukin 1α Is Critical for Resistance against Highly Virulent Aspergillus fumigatus Isolatesen_US
mus.citation.journaltitleInfection & Immunityen_US
mus.identifier.categoryLife Sciences & Earth Sciencesen_US
mus.relation.collegeCollege of Agricultureen_US
mus.relation.collegeCollege of Letters & Scienceen_US
mus.relation.departmentMicrobiology & Immunology.en_US
mus.relation.universityMontana State University - Bozemanen_US
mus.contributor.orcidObar, Joshua J.|0000-0003-4068-7911en_US
mus.contributor.orcidCramer, Robert A.|0000-0001-5503-5006en_US

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