Chapter 32 : Innate and Acquired Cellular Immunity to Fungi

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Studies with have provided a paradigm that incorporates contributions from both the fungus and the host to explain the theme of the origin and maintenance of virulence for commensals. The majority of fungi are detected and destroyed within hours by innate defense mechanisms. Thus, innate and adaptive immune responses are intimately linked and controlled by sets of molecules and receptors that act to generate the most effective form of immunity for protection against fungal pathogens. Traditionally, the innate defense mechanisms used by the host against fungi have been considered of two types, constitutive and inducible, although the recent finding that the expression of constitutive mechanisms may be regulated by toll-like receptors (TLRs) signaling highlights the interdependency of the two systems. The different impact of TLRs on the occurrence of the innate and adaptive Th immunity to fungi is consistent with the ability of each individual TLR to activate specialized antifungal effector functions on phagocytes and dendritic cells (DCs). Binding and internalization of fungi by polymorphonuclear leukocytes (PMNs) may occur through different receptors, of which CR3 and FcγR, presumably FcγRI or FcγRI, are the most effective in terms of phagocytosis and fungicidal activity. On contact with a pathogen, cells of the innate immune system release a battery of chemokines and cytokines. The therapeutic efficacy of antifungals is limited without the help of host immune reactivity. Various cytokines, including chemokines and growth factors, have proved to be beneficial in experimental and human refractory fungal infections.

Citation: Romani L. 2006. Innate and Acquired Cellular Immunity to Fungi, p 471-486. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch32
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Image of Figure 1.
Figure 1.

Interface between innate and adaptive immunity to fungi. Essential to the successful removal of pathogens is the early recognition of fungi by components of the innate immune systems. These involve the complement systems, opsonins, antibodies, and specialized receptors such as TLRs expressed on NK cells and phagocytes that recognize specific fungus-derived molecular structures. Successful engagement of some of these pathways leads to an inflammatory response with destruction of the pathogen alongside the establishment of DC and T-cell and/or B-cell interactions. A well-orchestrated innate and adaptive immune response will lead to pathogen eradication and host immunity (white box). Failure to efficiently discriminate self from nonself in innate as well as adaptive immunity can lead to pathogen proliferation and ultimately to dysregulated immunity such as autoimmunity, allergy, and sepsis (dark gray box).

Citation: Romani L. 2006. Innate and Acquired Cellular Immunity to Fungi, p 471-486. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch32
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Image of Figure 2.
Figure 2.

The crucial role for the IFN-γ/IDO-dependent metabolic pathway in infection. The production of IFN-γ is placed squarely at the host/pathogen interface, where IDO activation exerts a fine control over fungal morphology as well as the inductive and effector pathways of immune resistance to the fungus.

Citation: Romani L. 2006. Innate and Acquired Cellular Immunity to Fungi, p 471-486. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch32
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Table 1.

Functional plasticity of DCs at the fungus/immune system interface

Citation: Romani L. 2006. Innate and Acquired Cellular Immunity to Fungi, p 471-486. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch32

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