Interleukin-17-induced protein lipocalin 2 is dispensable for immunity to oral candidiasis.

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 those of the Th17 subset. Interleukin-17 (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; neutrophil gelatinase-associated lipocalin [NGAL]) is an antimicrobial host defense factor 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 Escherichia coli and Klebsiella pneumoniae. The role of Lcn2 in mediating immunity to fungi is poorly defined. Accordingly, in this study, we evaluated the role of Lcn2 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 with defective IL-17 signaling (IL-17RA(-/-) or Act1(-/-) mice). However, Lcn2(-/-) mice were completely resistant to OPC, comparably to wild-type (WT) mice. Moreover, Lcn2 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.

• Authors: Maria Carolina Ferreira, Natasha Whibley, Anna J Mamo, Ulrich Siebenlist, Yvonne R Chan, Sarah L Gaffen
• Journal: Infection and immunity (Infect Immun) Vol. 82 Issue 3 Pg. 1030-5 (Mar 2014) ISSN: 1098-5522 [Electronic] United States
• PMID: 24343647 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Acute-Phase Proteins
• Interleukin-17
• Lipocalin-2
• Lipocalins
• Oncogene Proteins
• Receptors, Interleukin-17
• Lcn2 protein, mouse

Topics

• Acute-Phase Proteins (genetics, immunology, metabolism)
• Animals
• Candida albicans (immunology)
• Candidiasis, Oral (genetics, immunology, metabolism, microbiology)
• Interleukin-17 (genetics, immunology, metabolism)
• Lipocalin-2
• Lipocalins (genetics, immunology, metabolism)
• Mice
• Mice, Inbred C57BL
• Mouth Mucosa (immunology, metabolism, microbiology)
• Mucous Membrane (immunology, metabolism, microbiology)
• Oncogene Proteins (genetics, immunology, metabolism)
• Receptors, Interleukin-17 (genetics, immunology, metabolism)
• Up-Regulation (genetics, immunology)