Chapter 35 : Intracellular Pathogenesis of

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This chapter reviews what is known about the strategies used by yeasts to survive within human and animal murine macrophages, how murine macrophages become activated, and the mechanisms by which activated murine macrophages kill yeasts. The interaction of with dendritic cells (DC) is also discussed, as are the different roles that murine macrophages and DC may play in the development of cell-mediated immunity to . Recent studies demonstrate that the ligand on the surface of yeasts and conidia that is recognized by murine macrophages CD18 receptors is heat shock protein 60 (hsp60). Once inside the phagosome, must avoid the microbicidal armamentarium of the murine macrophages that consists of the generation of toxic oxygen molecules (respiratory burst) and lysosomal hydrolases (phagolysosomal fusion [PL fusion]). Intracellular pathogens have evolved numerous strategies to avoid these murine macrophages defense mechanisms, including inhibition of phagolysosomal fusion (PL) (e.g., ), escaping from the phagocytic vacuole into the cytoplasm (e.g., ), and initiating phagocytosis without stimulating the respiratory burst (e.g., Toxoplasma gondii). The intracellular replication of yeasts in human monocytes and murine macrophages occurs at a similar rate even though murine macrophages have lost their myeloperoxidase and are unable to make toxic oxygen metabolites distal to HO. In contrast to our knowledge of murine immunology, the cytokines required to activate human murine macrophages fungistatic or fungicidal activity against remain obscure.

Citation: Newman S. 2006. Intracellular Pathogenesis of , p 527-536. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch35

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Tumor Necrosis Factor alpha
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Image of Figure 1.
Figure 1.

Differential response of human and murine Mϕ to yeasts. Upon ingestion of yeasts, the respiratory burst of murine Mϕ is not stimulated, but PL fusion does occur. In contrast, there is production of toxic oxygen radicals by human Mϕ, but minimal PL fusion. Further, murine Mϕ are activated by IFN-γ to inhibit the intracellular replication of yeasts, whereas IFN-γ does not activate human Mϕ. In both human and murine Mϕ, the intraphagosomal pH is maintained at 6.5.

Citation: Newman S. 2006. Intracellular Pathogenesis of , p 527-536. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch35
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Image of Figure 2.
Figure 2.

Differential recognition and response of human Mϕ and DC to yeasts. Mϕ utilize the CD18 receptor family to recognize the ligand Hsp60 on the surface of yeasts. Upon ingestion of the yeasts, PL fusion is blocked and the yeasts replicate. In contrast, DC use the VLA-5 receptor to recognize cyclophilin A on the surface of yeasts. Upon ingestion of the yeasts, PL fusion takes place and the yeasts are killed and degraded.

Citation: Newman S. 2006. Intracellular Pathogenesis of , p 527-536. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch35
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