IL-25 Receptor Signaling Modulates Host Defense against Cryptococcus neoformans Infection.

Abstract

Cryptococcal meningitis is one of the most common life-threatening diseases caused by Cryptococcus infection. Increasing evidence indicates that type 2 immunity is associated with disease progression by promoting fungal growth and dissemination. However, factors that govern this pathogenic response during infection are still elusive. In this study, we investigated the role of IL-25, one of the type 2-inducing cytokines produced by epithelial cells, in contributing to the pathogenesis of cryptococcosis. We found that pulmonary but not systemic infection with a high-virulence strain of C. neoformans significantly induced pulmonary IL-25 expression in the lungs but not brains. In response to pulmonary infection, mice deficient in the surface IL-17 receptor B, a component of the IL-25R, exhibited improved survival with a decreased brain fungal burden. The absence of IL-25R signaling diminished the type 2 and enhanced the type 1 immune response that directed macrophage polarization toward M1 macrophages. Interestingly, Cryptococcus-mediated IL-25 signaling suppressed the expression of cytokines and chemokines associated with protection in the brain, including Ifng, Il1b, Ip10, and Nos2, without affecting brain cellular inflammation and microglia cell activation. Il17rb-/- mice receiving cryptococcal-specific CD4+ T cells from wild-type had a shorter survival time with higher fungal burden within the brain and an elevated expression of M2 macrophage markers than those receiving cryptococcal-specific CD4+ T cells from Il17rb-/- mice. Taken together, our data indicated that IL-25 signaling subverts the induction of protective immunity and amplifies the type 2 immune response that may favor the development of cryptococcal disease and the fungal dissemination to the CNS.

• Authors: Adithap Hansakon, Siranart Jeerawattanawart, Kovit Pattanapanyasat, Pornpimon Angkasekwinai
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 205 Issue 3 Pg. 674-685 (08 01 2020) ISSN: 1550-6606 [Electronic] United States
• PMID: 32561567 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 by The American Association of Immunologists, Inc.

Chemical References

• Cytokines
• Receptors, Interleukin
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse

Topics

• Animals
• Cryptococcosis (immunology)
• Cryptococcus neoformans (immunology)
• Cytokines (immunology)
• Female
• Macrophages (immunology)
• Mice
• Mice, Inbred BALB C
• Nitric Oxide Synthase Type II (immunology)
• Receptors, Interleukin (immunology)
• Signal Transduction (immunology)
• Th1 Cells (immunology)
• Th2 Cells (immunology)