IL-17 signaling in host defense against Candida albicans
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UNIVERSITY OF PITTSBURGH IMMUNOLOGY 2011
IL-17 signaling in host defense against Candida albicans Sarah L. Gaffen • Nydiaris Herna´ndez-Santos Alanna C. Peterson
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Sarah L. Gaffen Published online: 30 June 2011 Ó Springer Science+Business Media, LLC 2011
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Abstract The discovery of the Th17 lineage in 2005 triggered a major change in how immunity to infectious diseases is viewed. Fungal infections, in particular, have long been a relatively understudied area of investigation in terms of the host immune response. Candida albicans is a commensal yeast that colonizes mucosal sites and skin. In healthy individuals, it is non-pathogenic, but in conditions of immune deficiency, this organism can cause a variety of infections associated with considerable morbidity. Candida can also cause disseminated infections that have a high mortality rate and are a major clinical problem in hospital settings. Although immunity to Candida albicans was long considered to be mediated by Th1 cells, new data in both rodent models and in humans have revealed an essential role for the Th17 lineage, and in particular its signature cytokine IL-17. Keywords
IL-17 Th17 Candida albicans Fungal infections Cytokine
Abbreviations OPC Oropharygeal candidiasis CMC Chronic mucocutaneous candidiaisis HIES Hyper-IgE Syndrome APS-1 Autoimmune polyendocrine syndrome-1 AMP Antimicrobial peptide PRR Pattern recognition receptor AR Autosomal recessive LOF Loss of function
Nydiaris Herna´ndez-Santos and Alanna C. Peterson contributed equally to this article. S. L. Gaffen (&) N. Herna´ndez-Santos A. C. Peterson Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, BST S703, 3500 Terrace St, Pittsburgh, PA 15216, USA e-mail: [email protected]
Introduction Th17 cells and IL-17: a brief history Effector CD4? T helper cells (Th) coordinate immune responses through the production of cytokines, which in turn are instrumental in shaping the nature of the response that is generated. In 1986, it was recognized that there are at least two distinct categories of Th cells that induce different types of immune responses, termed ‘‘Th1’’ and ‘‘Th2’’ (Fig. 1) [1]. In contrast to generation of the antigenspecific TCR, these subsets are not pre-committed, but rather are generated depending on the microenvironment. Over time, it became clear that naı¨ve Th cells exposed to IL-12 progressed along the Th1 differentiation pathway leading to secretion of IFNc, a process dependent on the transcription factors STAT-4 and T-bet. Conversely, IL-4 and the transcription factors STAT-6 and GATA-3 trigger a differentiation program leading to Th2 generation, characterized by secretion of IL-4. These pathways are mutually inhibitory and self-reinforcing. In 2005, a third subset was identified that was clearly neither Th1 nor Th2. This Th lineage could be generated in
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Fig. 1 Diagram of major Th effector subsets. T cell precursors (Thp) can be induced to differentiate into different subsets depending on the cytokine enviro
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