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Chapter 76 : Inflammatory Immune Response to Cytosolic Flagellin Protects Mice from Infection

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Inflammatory Immune Response to Cytosolic Flagellin Protects Mice from Infection, Page 1 of 2

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Abstract:

has earned a reputation as a public scourge, and rightly so. With the goal of identifying the molecular basis of pathogenesis, investigators quickly turned to animal models. By exploiting the observation that susceptibility to behaves as a single Mendelian trait, the Dietrich and Gross laboratories identified as a critical determinant of mouse resistance to this pathogen. Based on these and other pioneering pathology and immunology studies in the 1980s and 1990s, workers in the field today continue to depend on small animal models to investigate the host-pathogen interactions that govern the outcome of infection. Flagellar-based motility is mediated by a sophisticated organelle whose components are strictly regulated and whose assembly is carefully orchestrated. Extracellular flagellin is recognized by a receptor on the surface of eukaryotic cells, Toll-like receptor 5 ( TLR-5; 17). Knowing that bacterial flagellins trigger a rapid, proinflammatory innate immune response, the authors postulated that lysis of macrophages by motile was not a pathogen tactic, but rather a host defense. can induce apoptosis in numerous cell types, including human peripheral blood monocytes, human monocyte, epithelial and T cell lines, and mouse alveolar macrophages and epithelial cells. If the macrophage response to flagellin is indeed a host mechanism to combat infection, the authors postulated that that lack flagellin would escape the Naip5.

Citation: S. Swanson M, G. Byrne B, W. Whitfield N, T. Fuse E, Tateda K, B. Molofsky A. 2006. Inflammatory Immune Response to Cytosolic Flagellin Protects Mice from Infection, p 313-320. In Cianciotto N, Kwaik Y, Edelstein P, Fields B, Geary D, Harrison T, Joseph C, Ratcliff R, Stout J, Swanson M (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555815660.ch76

Key Concept Ranking

Tumor Necrosis Factor alpha
0.46881172
White Blood Cells
0.4659275
Type IV Secretion Systems
0.45142373
Innate Immune System
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0.46881172
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Figures

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FIGURE 1

requires fla-gellin but not motility to induce macrophage death. After centrifugation with two-fold dilutions of the strains indicated, A/J mouse macrophages and microbes were incubated for 1 h, and then viability was determined by Alamar Blue reduction. Shown are mean percent of viable macrophages ± standard error pooled from three or more experiments in multiplicity of infection bins of two-fold dilutions; the middle value for each bin is indicated. WT, wild-type strain Lp02; mutants lack type IV secretion but are fully motile; mutants lack the structural protein flagellin; mutants secrete but do not assemble flagellin; mutants lack motility and type IV secretion but secrete flagellin protein.

Citation: S. Swanson M, G. Byrne B, W. Whitfield N, T. Fuse E, Tateda K, B. Molofsky A. 2006. Inflammatory Immune Response to Cytosolic Flagellin Protects Mice from Infection, p 313-320. In Cianciotto N, Kwaik Y, Edelstein P, Fields B, Geary D, Harrison T, Joseph C, Ratcliff R, Stout J, Swanson M (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555815660.ch76
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Image of FIGURE 2
FIGURE 2

Secretion of IL-1β by macrophages in response to is controlled by Naip5 and caspase-1. After infecting the macrophages shown for 1 h with wild-type at the multiplicity of infection indicated, secreted interleukin-1p was quantified. Where indicated, macrophages were treated for 1 h before and during the infection with 100 μM Ac-YVAD-cmk, an inhibitor of caspase-1.

Citation: S. Swanson M, G. Byrne B, W. Whitfield N, T. Fuse E, Tateda K, B. Molofsky A. 2006. Inflammatory Immune Response to Cytosolic Flagellin Protects Mice from Infection, p 313-320. In Cianciotto N, Kwaik Y, Edelstein P, Fields B, Geary D, Harrison T, Joseph C, Ratcliff R, Stout J, Swanson M (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555815660.ch76
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Image of FIGURE 3
FIGURE 3

Model for the innate immune response of mice to infection. See text for details.

Citation: S. Swanson M, G. Byrne B, W. Whitfield N, T. Fuse E, Tateda K, B. Molofsky A. 2006. Inflammatory Immune Response to Cytosolic Flagellin Protects Mice from Infection, p 313-320. In Cianciotto N, Kwaik Y, Edelstein P, Fields B, Geary D, Harrison T, Joseph C, Ratcliff R, Stout J, Swanson M (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555815660.ch76
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References

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Tables

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TABLE 1

Recognition of flagellin by mouse macrophages restricts infection

Citation: S. Swanson M, G. Byrne B, W. Whitfield N, T. Fuse E, Tateda K, B. Molofsky A. 2006. Inflammatory Immune Response to Cytosolic Flagellin Protects Mice from Infection, p 313-320. In Cianciotto N, Kwaik Y, Edelstein P, Fields B, Geary D, Harrison T, Joseph C, Ratcliff R, Stout J, Swanson M (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555815660.ch76

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