AUTHOR=Caffrey-Carr Alayna K. , Hilmer Kimberly M. , Kowalski Caitlin H. , Shepardson Kelly M. , Temple Rachel M. , Cramer Robert A. , Obar Joshua J. 

TITLE=Host-Derived Leukotriene B4 Is Critical for Resistance against Invasive Pulmonary Aspergillosis

JOURNAL=Frontiers in Immunology

VOLUME=8

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.01984

DOI=10.3389/fimmu.2017.01984

ISSN=1664-3224

ABSTRACT=<p><italic>Aspergillus fumigatus</italic> is a mold that causes severe pulmonary infections. Our knowledge of how immune competent hosts maintain control of fungal infections while constantly being exposed to fungi is rapidly emerging. It is known that timely neutrophil recruitment to and activation in the lungs is critical to the host defense against development of invasive pulmonary aspergillosis, but the inflammatory sequelae necessary remains to be fully defined. Here, we show that 5-Lipoxygenase (5-LO) and Leukotriene B<sub>4</sub> (LTB<sub>4</sub>) are critical for leukocyte recruitment and resistance to pulmonary <italic>A. fumigatus</italic> challenge in a fungal-strain-dependent manner. 5-LO activity was needed in radiosensitive cells for an optimal anti-fungal response and <italic>in vivo</italic> LTB<sub>4</sub> production was at least partially dependent on myeloid-derived hypoxia inducible factor-1α. Overall, this study reveals a role for host-derived leukotriene synthesis in innate immunity to <italic>A. fumigatus</italic>.</p>