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Chapter 23 : Acquired Immunity: Fungal Infections
Category: Immunology; Clinical Microbiology
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The most common of the human diseases caused by fungi are the opportunistic fungal infections that occur in patients with defective immunity. This chapter attempts to position the new findings on acquired immunity and fungi within the conceptual framework of a two-component antifungal response that includes resistance and tolerance. Resistance and tolerance are two types of host defense mechanisms that increase fitness in response to fungi. The enzyme indoleamine 2,3-dioxygenase (IDO) and tryptophan metabolites contribute to immune homeostasis by inducing Tregs and taming heightened inflammatory responses. The new entry, the Th17 pathway, playing an inflammatory role previously attributed to uncontrolled Th1 cell reactivity and Tregs and capable of fine-tuning protective antimicrobial immunity in order to minimize harmful immune pathology, have become an integral component of the immune response to fungi. In their capacity to induce Tregs and inhibit Th17, IDO and kynurenines pivotally contribute to cell lineage decision in experimental fungal infections and reveal an unexpected potential in the control of inflammation, allergy, and Th17-driven inflammation in these infections. Serological and skin reactivity surveys indicate the development of acquired cell-mediated immunity (CMI) to fungi. A number of clinical observations suggest an inverse relationship between interferon (IFN)-γ and interleukin (IL)-10 production in patients with fungal infections. The implication for IDO in immunoregulation in fungal infections has several important implications.
The pathogenesis of typical fungal infections.
Th cell subsets in response to fungi. The figure shows the orchestration of Th/Treg cell subsets differentiation, their transcription factors, cytokine production, and possible effector/regulatory functions in fungal infections. DCs, dendritic cells. See text for details.
Regulatory T cells in fungal infections a
Prospectives on anti-inflammatory strategies in fungal diseases a