Ferreira, Maria Carolina, Whibley, Natasha, Mamo, Anna J, Siebenlist, Ulrich, Chan, Yvonne and Gaffen, Sarah L (2014) The IL-17-induced gene Lipocalin 2 is dispensable for immunity to oral candidiasis. Infection and immunity, 82 (3). pp. 1030-1035. ISSN 1098-5522; 0019-9567

Abstract

Oropharyngeal candidiasis (OPC, thrush) is an opportunistic fungal infection caused by the commensal microbe Candida albicans. Immunity to OPC is strongly dependent on CD4+ T cells, particularly of the Th17 subset. IL-17-deficiency in mice or humans leads to chronic mucocutaneous candidiasis, but the specific downstream mechanisms of IL-17-mediated host defense remain unclear. Lipocalin-2 (Lcn2, 24p3, NGAL) is an antimicrobial host defense protein produced in response to inflammatory cytokines, particularly IL-17. Lcn2 plays a key role in preventing iron acquisition by bacteria that use catecholate-type siderophores, and lipocalin 2-/- mice are highly susceptible to infection by E. coli and Klebsiella pneumonia. The role of Lcn2 in mediating immunity to fungi is undefined. Accordingly, in this study we evaluated the role of 24p3 in immunity to oral infection with C. albicans. Lcn2 is strongly upregulated following oral infection with C. albicans, and its expression is almost entirely abrogated in mice defective in IL-17 signaling. However, Lcn2-/- mice were completely resistant to OPC, comparable to WT mice. Moreover, Lcn 2-deficiency mediated protection from OPC induced by steroid immunosuppression. Therefore, despite its potent regulation during C. albicans infection, Lcn2 is not required for immunity to mucosal candidiasis.

Item Type:	Article
Date Deposited:	07 Jan 2017 00:45
Last Modified:	07 Jan 2017 00:45
URI:	https://oak.novartis.com/id/eprint/20294