ArticlePLoS pathogens2014
Myeloid derived hypoxia inducible factor 1-alpha is required for protection against pulmonary Aspergillus fumigatus infection.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
57 citing papers in PubMed, 78 citations in OpenAlex.
- Article
- Keratinocyte HIF-1α Orchestrates Imiquimod-Induced Psoriasiform Inflammation by Promoting Type 3 Inflammation.Biomedicines · 2025Article
- Article
- HIF-α signaling regulates the macrophage inflammatory response duringFrontiers in immunology · 2025Article
- IFN Receptor 2 Regulates TNF-α-Mediated Damaging Inflammation during Aspergillus Pulmonary Infection.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Multiple roles for hypoxia inducible factor 1-alpha in airway epithelial cells during mucormycosis.Nature communications · 2024Article
- Recent Advances in Understanding the Human Fungal Pathogen Hypoxia Response in Disease Progression.Annual review of microbiology · 2023Review
- Novel Host Pathways Govern Epithelial Cell Invasion of Aspergillus fumigatus.Microbiology spectrum · 2023Article
- Dysregulated Pulmonary Inflammatory Responses Exacerbate the Outcome of Secondary Aspergillosis Following Influenza.bioRxiv : the preprint server for biology · 2023Article
- Could the Lung Be a Gateway for Amphotericin B to Attack the Army of Fungi?Pharmaceutics · 2022Review
- Targeting immunometabolism in host-directed therapies to fungal disease.Clinical and experimental immunology · 2022Review
- Transfusable neutrophil progenitors as cellular therapy for the prevention of invasive fungal infections.Journal of leukocyte biology · 2022Article
- Pathogenesis of Respiratory Viral and Fungal Coinfections.Clinical microbiology reviews · 2022Review
- Hypoxia inducible-factor 1 alpha regulates neutrophil recruitment during fungal-elicited granulomatous inflammation.Frontiers in cellular and infection microbiology · 2022Article
- Myeloid hypoxia-inducible factor HIF1A provides cardio-protection during ischemia and reperfusionFrontiers in cardiovascular medicine · 2022Article
- Article
- Review
- Survey of the Transcription Factor Responses of Mouse Lung Alveolar Macrophages toPathogens (Basel, Switzerland) · 2021Article
- Aspergillus fumigatus tryptophan metabolic route differently affects host immunity.Cell reports · 2021Article
- Fungal Bioreporters to Monitor Outcomes of Aspergillus: Host-Cell Interactions.Methods in molecular biology (Clifton, N.J.) · 2021Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Hypoxia inducible factor 1α (HIF1α) is the mammalian transcriptional factor that controls metabolism, survival, and innate immunity in response to inflammation and low oxygen. Previous work established that generation of hypoxic microenvironments occurs within the lung during infection with the human fungal pathogen Aspergillus fumigatus. Here we demonstrate that A. fumigatus stabilizes HIF1α protein early after pulmonary challenge that is inhibited by treatment of mice with the steroid triamcinolone. Utilizing myeloid deficient HIF1α mice, we observed that HIF1α is required for survival and fungal clearance early following pulmonary challenge with A. fumigatus. Unlike previously reported research with bacterial pathogens, HIF1α deficient neutrophils and macrophages were surprisingly not defective in fungal conidial killing. The increase in susceptibility of the myeloid deficient HIF1α mice to A. fumigatus was in part due to decreased early production of the chemokine CXCL1 (KC) and increased neutrophil apoptosis at the site of infection, resulting in decreased neutrophil numbers in the lung. Addition of recombinant CXCL1 restored neutrophil survival and numbers, murine survival, and fungal clearance. These results suggest that there are unique HIF1α mediated mechanisms employed by the host for protection and defense against fungal pathogen growth and invasion in the lung. Additionally, this work supports the strategy of exploring HIF1α as a therapeutic target in specific immunosuppressed populations with fungal infections.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.