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Chapter 37 : Fungal Interactions with Leukocytes

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Abstract:

This chapter discusses host defenses in the lungs and the role played by fungal virulence factors in allowing the organism to survive inside the host and either cause disease or remain latent.. On inhalation from the environment, fungi first encounter the barrier defenses of the lungs (cough reflexes, airway secretions, and mucociliary action of the upper airway epithelium). Alveolar macrophages, dendritic cells (DC), and recruited neutrophils and monocytes compose the phagocytic cells of the pulmonary innate immune system. Secretion of TNF-α by innate immune cells is critical for the development of protective adaptive immunity. IFN- γ production is critical for clearance of fungal infections in the lungs by activating macrophages and other phagocytes to ingest and kill fungi. Taken together, these observations demonstrate the importance of Th1-cell production of IFN-γ in pulmonary host defense against fungi. Susceptibility against pulmonary fungal infections in otherwise healthy individuals is associated with the production of Th2 cytokines such as IL-4, IL-5, and IL-10. The maturation state or phenotype of DC is perhaps the most important regulatory step in the development of T-cell immunity in the lungs. Many of these moieties can stimulate inflammatory cytokine production by lung leukocytes when administered in pure form. Although B cells are discussed last in the list of cells that interact with fungi, their role in modulating host defense against fungi cannot be understated. The majority of human fungal pathogens are opportunistic ubiquitous organisms, causing disease only under permissive conditions.

Citation: Noverr M, Lindell D, Toews G, Huffnagle G. 2006. Fungal Interactions with Leukocytes, p 555-563. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch37

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Figure 1

Model for how the gut microbiota might regulate pulmonary immune responses. Antigen (Ag) initially comes in contact with the lung during infection (microbe + Ag) or inhalation (Ag). This antigen is captured by cells of the innate immune system, which then stimulate adaptive immune responses in secondary lymphoid organs such as the lymph nodes or spleen. Antigen-specific T cells are recruited to the lungs on subsequent antigen exposure. To prevent the development of allergic inflammatory (Th2) responses to inhaled antigens that are noninfectious (pollens) or of extremely low infectivity (mold spores), regulatory T-cell networks produce anti-inflammatory mediators that down-regulate inflammatory T-cell activities. Inhaled antigens are also swallowed because the anatomy of the sinuses and upper airways is designed to trap environmental antigens (aerosols, microparticulates, and macroparticulates) in the mucus layer and then “sweep” them into the throat, where they are swallowed. Swallowed Ags are then acquired by DC in the gut. Under noninflammatory conditions, these DC promote the development of a regulatory T-cell response to the Ag, which can control reexposure responses in the lungs in the absence of infection. The precise mechanism by which the gastrointestinal microbiota balance helps to maintain the T-cell regulatory networks that mediate oral tolerance is unknown.

Citation: Noverr M, Lindell D, Toews G, Huffnagle G. 2006. Fungal Interactions with Leukocytes, p 555-563. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch37
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