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Identification of endogenous pro‐resolving mechanisms in a murine model of cryptococcal pneumonia
Author(s) -
Colby Jennifer Kay,
Gott Katherine,
Wilder Julie,
Levy Bruce D.
Publication year - 2013
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/fasebj.27.1_supplement.645.12
Subject(s) - bronchoalveolar lavage , lipoxin , cryptococcus neoformans , immunology , inflammation , lung , receptor , pathogen , microbiology and biotechnology , biology , chemistry , medicine , biochemistry
Lipoxins (LX) are potent anti‐inflammatory and pro‐resolving lipid mediators that augment host defense. We hypothesized that established mouse strain‐dependent differences in clearance of the fungal pathogen Cryptococcus neoformans ( Cne) were linked to alterations in LX synthesis and signaling. C.B‐17 and C57BL/6 (B6) mice were inoculated intranasally with 5000 cfu Cne (day 0). C.B‐17 but not B6 mice effectively cleared Cne from the lungs. Leukocyte counts revealed fewer lung macrophages, but increased eosinophils and activated CD4+ T cells in lung and bronchoalveolar lavage fluids (BALFs) at d7, 14, 21 and 28 after infection. BALF levels of LXA 4 as measured by ELISA were highest at d14 and d28 in B6 and d18 and 21 in C.B‐17 (p≤0.025 vs. uninfected). Similar patterns were observed for 15‐epi‐LXA 4 . Comparative qPCR analysis of naive and d14 lungs showed Cne‐ induced increases in expression of Alox15 (15‐lipoxygenase‐1) at d14 (both strains), Alox5 (5‐lipoxygenase) (B6 only), and Fpr2 (lipoxin receptor, ALX) (C.B‐17 only). In summary, altered cellular immunity in B6 mice is associated with differences in LX synthesis and LX receptor expression. This experimental system provides a window into regulation of pathogen‐mediated inflammation and clearance and highlights important relationships between lipoxins and lung host defense.