{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T01:33:08Z","timestamp":1785202388628,"version":"3.55.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T00:00:00Z","timestamp":1585699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Development of invasive aspergillosis correlates with impairments in innate immunity. We and others have recently shown that arachidonic acid metabolism pathways, specifically the cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) pathways, participate in the induction of protective innate immune responses during invasive aspergillosis. Based on the high degree of cooperation and interconnection within the eicosanoid network, we hypothesized that 12\/15-LOX is also active during invasive aspergillosis. We report in this study that mice deficient in the gene encoding 12\/15-LOX (Alox15) are profoundly susceptible to invasive aspergillosis. Decreased survival correlated with increased fungal burden and evidence of increased lung damage. These defects were associated with very early (6 and 12 h) 12\/15-LOX\u2013dependent inflammatory cytokine (IL-1\u03b1, IL-1\u03b2, and TNF-\u03b1) and chemokine (CCL3 and CCL4) production. Neutrophil levels in the lung were blunted in the absence of 12\/15-LOX, although neutrophil antifungal activity was intact. However, lower neutrophil levels in the lungs of Alox15\u2212\/\u2212 mice were not a result of impaired recruitment or survival; rather, Alox15\u2212\/\u2212 mice demonstrated impaired neutrophil granulopoiesis in the bone marrow intrinsically and after fungal exposure. Employing a lower inoculum to allow for better survival allowed the identification of 12\/15-LOX\u2013dependent induction of IL-17A and IL-22. Impaired IL-17A and IL-22 production correlated with reduced invariant NKT cell numbers as well as lower IL-23 levels. Together, these data indicate that 12\/15-LOX is a critical player in induction of the earliest aspects of the innate immune response to Aspergillus fumigatus.<\/jats:p>","DOI":"10.4049\/jimmunol.1900808","type":"journal-article","created":{"date-parts":[[2020,2,26]],"date-time":"2020-02-26T19:59:23Z","timestamp":1582747163000},"page":"1849-1858","source":"Crossref","is-referenced-by-count":16,"title":["12\/15-Lipoxygenase Deficiency Impairs Neutrophil Granulopoiesis and Lung Proinflammatory Responses to <i>Aspergillus fumigatus<\/i>"],"prefix":"10.1093","volume":"204","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0824-3552","authenticated-orcid":false,"given":"Joseph J","family":"Mackel","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaleesa M","family":"Garth","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0884-2061","authenticated-orcid":false,"given":"Jonathan P","family":"Blackburn","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MaryJane","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine, Tulane University , New Orleans, LA 70112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad","family":"Steele","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine, Tulane University , New Orleans, LA 70112"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,4,1]]},"reference":[{"key":"2025030417511268500_r1","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.idc.2018.04.006","article-title":"Mold infections in solid organ transplant recipients","volume":"32","author":"Lemonovich","year":"2018","journal-title":"Infect. 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