IL-17 regulates systemic fungal immunity by controlling the functional competence of NK cells.

Abstract

Interleukin 17 (IL-17)-mediated immunity plays a key role in protection from fungal infections in mice and man. Here, we confirmed that mice deficient in the IL-17 receptor or lacking the ability to secrete IL-17 are highly susceptible to systemic candidiasis, but we found that temporary blockade of the IL-17 pathway during infection in wild-type mice did not impact fungal control. Rather, mice lacking IL-17 receptor signaling had a cell-intrinsic impairment in the development of functional NK cells, which accounted for the susceptibility of these mice to systemic fungal infection. NK cells promoted antifungal immunity by secreting GM-CSF, necessary for the fungicidal activity of neutrophils. These data reveal that NK cells are crucial for antifungal defense and indicate a role for IL-17 family cytokines in NK cell development. The IL-17-NK cell axis may impact immunity against not only fungi but also bacteria, viruses, and tumors.

• Authors: Eva Bär, Paul G Whitney, Kathrin Moor, Caetano Reis e Sousa, Salomé LeibundGut-Landmann
• Journal: Immunity (Immunity) Vol. 40 Issue 1 Pg. 117-27 (Jan 16 2014) ISSN: 1097-4180 [Electronic] United States
• PMID: 24412614 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Interleukin-17
• Receptors, Interleukin-17
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Animals
• Candidiasis (genetics, immunology)
• Cell Differentiation
• Cells, Cultured
• Cytotoxicity, Immunologic
• Disease Susceptibility
• Granulocyte-Macrophage Colony-Stimulating Factor (metabolism)
• Interleukin-17 (genetics, metabolism)
• Killer Cells, Natural (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Neutrophils (immunology)
• Receptors, Interleukin-17 (genetics, metabolism)
• Signal Transduction (genetics)