Journal article
Sterilizing immunity in the lung relies on targeting fungal apoptosis-like programmed cell death
Science (American Association for the Advancement of Science), Vol.357(6355), pp.1037-1041
09/08/2017
DOI: 10.1126/science.aan0365
PMCID: PMC5628051
PMID: 28883073
Abstract
Humans inhale mold conidia daily and typically experience lifelong asymptomatic clearance. Conidial germination into tissue-invasive hyphae can occur in individuals with defects in myeloid function, although the mechanism of myeloid cell-mediated immune surveillance remains unclear. By monitoring fungal physiology in vivo, we demonstrate that lung neutrophils trigger programmed cell death with apoptosis-like features in
conidia, the most prevalent human mold pathogen. An antiapoptotic protein, AfBIR1, opposes this process by inhibiting fungal caspase activation and DNA fragmentation in the murine lung. Genetic and pharmacologic studies indicate that AfBIR1 expression and activity underlie conidial susceptibility to NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase-dependent killing and, in turn, host susceptibility to invasive aspergillosis. Immune surveillance exploits a fungal apoptosis-like programmed cell death pathway to maintain sterilizing immunity in the lung.
Details
- Title: Subtitle
- Sterilizing immunity in the lung relies on targeting fungal apoptosis-like programmed cell death
- Creators
- Neta Shlezinger - Memorial Sloan Kettering Cancer CenterHenriette Irmer - University of GöttingenSourabh Dhingra - Dartmouth CollegeSarah R Beattie - Dartmouth CollegeRobert A Cramer - Dartmouth CollegeGerhard H Braus - University of GöttingenAmir Sharon - Tel Aviv UniversityTobias M Hohl - Memorial Sloan Kettering Cancer Center
- Resource Type
- Journal article
- Publication Details
- Science (American Association for the Advancement of Science), Vol.357(6355), pp.1037-1041
- DOI
- 10.1126/science.aan0365
- PMID
- 28883073
- PMCID
- PMC5628051
- NLM abbreviation
- Science
- ISSN
- 0036-8075
- eISSN
- 1095-9203
- Grant note
- R21 AI105617 / NIAID NIH HHS P30 GM106394 / NIGMS NIH HHS R01 AI093808 / NIAID NIH HHS P30 CA008748 / NCI NIH HHS R01 AI081838 / NIAID NIH HHS T32 GM008704 / NIGMS NIH HHS
- Language
- English
- Date published
- 09/08/2017
- Academic Unit
- Stead Family Department of Pediatrics; Infectious Disease (Pediatrics)
- Record Identifier
- 9984353841102771
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