Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis

By H. Conti, F. Shen, Namrata Nayyar, Eileen Stocum, Jianing N. Sun, M. Lindemann, A. Ho, J. H. Hai, Jeffrey J. Yu, Ji-Won Jung and 4 more. Journal of Experimental Medicine, 2009

1,050 citations recorded by the source corpus.

The commensal fungus Candida albicans causes oropharyngeal candidiasis (OPC; thrush) in settings of immunodeficiency. Although disseminated, vaginal, and oral candidiasis are all caused by C. albicans species, host defense against C. albicans varies by anatomical location. T helper 1 (Th1) cells have long been implicated in defense against candidiasis, whereas the role of Th17 cells remains controversial. IL-17 mediates inflammatory pathology in a gastric model of mucosal candidiasis, but is host protective in disseminated disease. Here, we directly compared Th1 and Th17 function in a model of OPC. Th17-deficient (IL-23p19−/−) and IL-17R–deficient (IL-17RA−/−) mice experienced severe OPC, whereas Th1-deficient (IL-12p35−/−) mice showed low fungal burdens and no overt disease. Neutrophil recruitment was impaired in IL-23p19−/− and IL-17RA−/−, but not IL-12−/−, mice, and TCR-αβ cells were more important than TCR-γδ cells. Surprisingly, mice deficient in the Th17 cytokine IL-22 were only mildly susceptible to OPC, indicating that IL-17 rather than IL-22 is vital in defense against oral candidiasis. Gene profiling of oral mucosal tissue showed strong induction of Th17 signature genes, including CXC chemokines and β defensin-3. Saliva from Th17-deficient, but not Th1-deficient, mice exhibited reduced candidacidal activity. Thus, the Th17 lineage, acting largely through IL-17, confers the dominant response to oral candidiasis through neutrophils and antimicrobial factors.

Subfields: Epidemiology, Immunology, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/9c71b87791b4a2e3d9fdac2719e0d6bc3488b514

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Epidemiology

1. Y. Iwakura
2. H. Ishigame
3. Shizuo Akira
4. Taro Kawai
5. R. Medzhitov

In Immunology

1. D. Cua
2. S. Gaffen
3. M. McGeachy
4. A. Garg
5. Y. Iwakura
6. H. Ishigame
7. Nilesh Amatya
8. S. Nakae

In Infectious Diseases

1. Shizuo Akira

Citations in the corpus

• IL-17 Signaling: The Yin and the Yang (2017, background): “IL-17 induces MCPIP1 mRNA (Zc3h12a) and protein in non-hematopoietic cells [74, 92, 93].”
• The IL-17 family of cytokines in health and disease (2019, background): “Host protection from oral Candida albicans infection is exquisitely reliant on IL-17 signaling, shown in both mouse and human settings (Bär et al., 2012; Conti et al., 2016; Conti et al., 2009; Puel et al., 2011a).”
• The light and dark sides of intestinal intraepithelial lymphocytes (2011, neutral): “Finally, recent data have highlighted the intriguing phenomena of plasticity of CD4 + effector and regulatory T cell”
• Dectin-2 recognition of alpha-mannans and induction of Th17 cell differentiation is essential for host defense against Candida albicans. (2010, background): “…681–691, May 28, 2010 ª2010 Elsevier Inc. Recently, it was reported that Th17 cells play an important role in the defense against C. albicans infection because IL-17RA-deficient mice and Th17 cell (IL-23p19)-deficient mice show increased susceptibility to mucosal candidiasis (Conti et al., 2009).”
• Functional specialization of interleukin-17 family members. (2011, background): “Il23a / and Il17ra / , but not Il12a / , mice are highly susceptible to oral candidiasis because of defective neutrophil recruitment and antimicrobial peptide production (Conti et al., 2009).”