Chapter 9 : Immunology of Invasive Candidiasis

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Invasive candidiasis is a life-threatening opportunistic infection and has emerged as a major cause of morbidity and mortality in critically ill patients. Until recently, was by far the predominant species, causing up to two-thirds of all cases of invasive candidiasis. This chapter highlights how the past several years have seen remarkable advances in understanding the basic cellular and immunological mechanisms underlying resistance to the fungus but also organ dysfunction and failure of recovery relating to invasive candidiasis. In experimental candidiasis, both defense mechanisms are activated through the delicate equilibrium between Th/Th17 cells and regulatory T cells (Tregs) limiting the consequences of the associated inflammatory pathology. The inflammatory response is initially mediated by cells of the innate immune system, followed by a later adaptive immune response, which is triggered by the signals originated by the innate immune system. The inflammatory response, initiated by cells of the innate immune system, is followed by adaptive immunity, which responds to, and at the same time regulates, signals emanating from the innate system. Indoleamine 2,3-dioxygenase (IDO) catalyzes the first and limiting step in the kynurenine pathway of tryptophan catabolism. Our increasing understanding of the basic mechanisms that dictate development and function of Th17 cells, as well as our better knowledge of how Th17/Tregs regulate each other as well as other immune and nonimmune cells, provides guidelines for rational design of novel immunomodulatory therapies that limit inflammation in order to stimulate an effective immune response.

Citation: Romani L. 2012. Immunology of Invasive Candidiasis, p 127-136. In Calderone R, Clancy C (ed), and Candidiasis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817176.ch9
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Resistance and tolerance to . The figure illustrates how the interplay between resistance, i.e., the ability to limit pathogen burden, and tolerance, i.e., the ability of the host to defend itself by limiting the damage caused by the infection, determines the ability of the host to resist fungal exposure and infection. An increased understanding of the two mechanisms in infections could aid the diagnosis and treatment of candidiasis (see text for further insights). doi:10.1128/9781555817176.ch9.f1

Citation: Romani L. 2012. Immunology of Invasive Candidiasis, p 127-136. In Calderone R, Clancy C (ed), and Candidiasis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817176.ch9
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Major PRRs involved in recognition of and activation of subsequent inflammatory/Th responses. The exploitation of the IDO/Treg axis for regulatory mechanisms may have allowed the commensal to coevolve with the mammalian immune system and to survive in conditions of high-threat inflammation (see text for a detailed description). doi:10.1128/9781555817176.ch9.f2

Citation: Romani L. 2012. Immunology of Invasive Candidiasis, p 127-136. In Calderone R, Clancy C (ed), and Candidiasis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817176.ch9
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IL-22 defines a novel immune pathway of antifungal resistance. DC-derived IL-23 promotes the production of IL-22 from cryptopatch CD3-NKp46 expressing RORγt, IL-23R, aryl hydrocarbon receptor, CCR5, and CCR7, indicating their similarity to gut RORγt NKp46 cells and cryptopatch lymphoid tissue inducer-like cells that are expanded by commensals. IL-22 targets epithelial cells for STAT3 activation and, together with IL-17A, for antimicrobial peptide production ( ). doi:10.1128/9781555817176.ch9.f3

Citation: Romani L. 2012. Immunology of Invasive Candidiasis, p 127-136. In Calderone R, Clancy C (ed), and Candidiasis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817176.ch9
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