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Candida albicans ‐induced leukotriene biosynthesis in neutrophils is restricted to the hyphal morphology
Author(s) -
Fischer Jana,
Gresnigt Mark S.,
Werz Oliver,
Hube Bernhard,
Garscha Ulrike
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202100516rr
Subject(s) - candida albicans , hypha , microbiology and biotechnology , biology , chemotaxis , leukotriene b4 , biosynthesis , inflammation , biochemistry , receptor , enzyme , immunology
Neutrophils are the most abundant leukocytes in circulation playing a key role in acute inflammation during microbial infections. Phagocytosis, one of the crucial defence mechanisms of neutrophils against pathogens, is amplified by chemotactic leukotriene (LT)B 4 , which is biosynthesized via 5‐lipoxygenase (5‐LOX). However, extensive liberation of LTB 4 can be destructive by over‐intensifying the inflammatory process. While enzymatic biosynthesis of LTB 4 is well characterized, less is known about molecular mechanisms that activate 5‐LOX and lead to LTB 4 formation during host–pathogen interactions. Here, we investigated the ability of the common opportunistic fungal pathogen Candida albicans to induce LTB 4 formation in neutrophils, and elucidated pathogen‐mediated drivers and cellular processes that activate this pathway. We revealed that C. albicans ‐induced LTB 4 biosynthesis requires both the morphological transition from yeast cells to hyphae and the expression of hyphae‐associated genes, as exclusively viable hyphae or yeast‐locked mutant cells expressing hyphae‐associated genes stimulated 5‐LOX by [Ca 2+ ] i mobilization and p38 MAPK activation. LTB 4 biosynthesis was orchestrated by synergistic activation of dectin‐1 and Toll‐like receptor 2, and corresponding signaling via SYK and MYD88, respectively. Conclusively, we report hyphae‐specific induction of LTB 4 biosynthesis in human neutrophils. This highlights an expanding role of neutrophils during inflammatory processes in the response to C. albicans infections.