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Inhaled Cryptococcus neoformans elicits allergic airway inflammation independent of Nuclear Factor Kappa B signalling in lung epithelial cells
Author(s) -
McDermott Andrew J.,
Tumey Tyler A.,
Huang Mingwei,
Hull Christina M.,
Klein Bruce S.
Publication year - 2018
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12853
Subject(s) - cryptococcus neoformans , biology , immunology , inflammation , lung , cytokine , nf κb , microbiology and biotechnology , medicine
Summary Pulmonary challenge with the ubiquitous fungus Cryptococcus neoformans results in allergic airway inflammation ( AAI ) characterized by robust recruitment of eosinophils and T cells producing type 2 cytokines to the lungs. Previous studies have demonstrated a critical role for Nuclear Factor Kappa B ( NF ‐ κ B) activation within lung epithelial cells ( LEC s) in driving AAI in response to protein allergens, yet the role of LEC ‐intrinsic NF ‐ κ B in promoting AAI following exposure to C. neoformans is poorly understood. To investigate the role of LEC ‐intrinsic NF ‐ κ B in promoting AAI following C. neoformans challenge, we used IKK ∆ LEC mice, which lack canonical NF ‐ κ B activation specifically within LEC s. IKK ∆ LEC and littermate control mice were intranasally challenged with 10 6 CFU of C. neoformans strain 52D, and lung tissues were collected at 7, 14 and 21 days post infection to assess the development of AAI . Notably, the absence of epithelial NF ‐ κ B signalling did not affect the magnitude or kinetics of lung eosinophilia when compared with the response in wild‐type control mice. The total numbers of lung T cells producing the type 2 cytokines interleukin‐5 and interleukin‐13 were also unchanged in IKK ∆ LEC mice. Furthermore, IKK ∆ LEC mice showed no defect in the recruitment of protective interferon‐ γ ‐producing CD 4 T cells to the lungs, fungal clearance, or host survival compared with control mice. Immunofluorescence imaging surprisingly revealed no evidence of nuclear localization of NF ‐ κ B in LEC s in response to C. neoformans challenge, indicating that NF ‐ κ B is not activated within these cells. Taken together, these data strongly suggest that NF ‐ κ B signalling within LEC s does not promote AAI observed in response to C. neoformans .