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Chapter 8 : Innate Immune Response and Inflammation: Roles in Pathogenesis and Protection ()

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Abstract:

Although spotted fever group rickettsiae (SFGR) and typhus group rickettsiae (TGR) represent two major antigenically defined and historically well-known subdivisions of pathogenic species, recent in-depth characterization by neighbor-joining phylodendrogramic analysis has distributed rickettsiae into ancestral, spotted fever, typhus, and transitional subgroups. Importantly, well-established and widely accepted in vivo models of infection closely mimicking the pathogenesis of Rocky Mountain spotted fever (RMSF) and epidemic typhus in humans employ infection of susceptible mouse strains with and , respectively. The endothelial cell responses to and signaling mechanisms that determine the interplay between the host and the unique rickettsial pathogen, which is capable of escaping immune surveillance to cause recrudescent infections, remain critically important but neglected areas of scientific inquiry. Thus, one of the major critical gaps in the understanding of rickettsial pathogenesis is the definition of the biological basis of rickettsial affinity and consequent interactions with vascular endothelium. infection induces a biphasic pattern of NF-ΚB activation in cultured human endothelial cells that is characterized by an early transient activation phase and a late sustained phase. There is increasing recognition that apoptosis, a tightly regulated process of altruistic suicide, plays a central role in complex interactions between an invading pathogen and host cell defense. First recognized for their ability to impede viral replication, interferons (IFNs) play a critical role in determining host survival in response to viral infection. During bacterial infections, IFN signaling defends the host by integrating early innate immune responses with later events.

Citation: Sahni S, Rydkina E, Simpson-Haidaris P. 2012. Innate Immune Response and Inflammation: Roles in Pathogenesis and Protection (), p 243-269. In Palmer G, Azad A (ed), Intracellular Pathogens II: . ASM Press, Washington, DC. doi: 10.1128/9781555817336.ch8

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Rocky Mountain Spotted Fever
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Endothelial cell functions under normal physiological conditions and inresponse to activation. PDGF, platelet-derived growth factor. doi:10.1128/9781555817336.ch8.f1

Citation: Sahni S, Rydkina E, Simpson-Haidaris P. 2012. Innate Immune Response and Inflammation: Roles in Pathogenesis and Protection (), p 243-269. In Palmer G, Azad A (ed), Intracellular Pathogens II: . ASM Press, Washington, DC. doi: 10.1128/9781555817336.ch8
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Image of FIGURE 2
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Summary of the current state of knowledge and potential future directions for investigations focused on interactions between pathogenic species and their preferred host niche, the vascular endothelium. doi:10.1128/9781555817336.ch8.f2

Citation: Sahni S, Rydkina E, Simpson-Haidaris P. 2012. Innate Immune Response and Inflammation: Roles in Pathogenesis and Protection (), p 243-269. In Palmer G, Azad A (ed), Intracellular Pathogens II: . ASM Press, Washington, DC. doi: 10.1128/9781555817336.ch8
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