Keane, Robert

Innate and adaptive immune responses Clinical Immunology: Principles and Practice. Chapter 3: Innate Immunity. Rich et al.

Martinon et al., 2009, Ann. Rev. Immunol. 27:229-265.

Duprez et al. Microbes & Infect. 11:1050

What Comprises the Innate Immune System in the CNS? Which CNS Cells Harbor Inflammasomes? What is the Regulation of the Innate Immune System After CNS Injury?

Primary vs . secondary injury

SCI induces increased expression and processing of IL-1  and IL-18

SCI induces increased expression of Caspase-1, -11 and ASC

de Rivero Vaccari JP, Lotocki G, Marcillo AE, Dietrich WD, Keane RW. (2008). J Neurosci. 28: 3404-3414

Association of NLRP1 Proteins in Neurons

Confocal images of spinal cord sections demonstrating anti-ASC antibody penetration into spinal cord neurons de Rivero Vaccari JP, Lotocki G, Marcillo AE, Dietrich WD, Keane RW. (2008). J Neurosci. 28: 3404-3414

ASC neutralization blocks NALP1 inflammasome activity de Rivero Vaccari JP, Lotocki G, Marcillo AE, Dietrich WD, Keane RW. (2008). J Neurosci. 28: 3404-3414

ASC neutralization improves histopathological outcome and decreases spinal cord lesion volume de Rivero Vaccari JP, Lotocki G, Marcillo AE, Dietrich WD, Keane RW. (2008). J Neurosci. 28: 3404-3414

de Rivero Vaccari JP, Lotocki G, Marcillo AE, Dietrich WD, Keane RW. (2008). J Neurosci. 28: 3404-3414 Anti-ASC treatment improves functional outcomes after SCI

ASC neutralization decreases NLRP1 inflammasome activity

ASC neutralization improves histopathological outcomes after TBI

Conclusions ,[object Object],[object Object],[object Object]

High Extracellular K+ Activates Caspase-1 in Neuronal and Astrocytic Cultures

Extracellular ATP Activates Caspase-1 in Human Astrocytic Cultures

ATP-Induced Caspase-1 Activation is Blocked by BBG and Probenecid

Pyroptosis is induced by the inflammasome, a multi-protein complex that stimulates caspase-1 cleavage ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Poly(dA:dT) Induces a Dose-Dependent Innate Immune Response in Cortical Neurons ,[object Object],[object Object]

Poly(dA:dT) Increases Expression of AIM2 Inflammasome Components ,[object Object],[object Object]

Poly(dA:dT) Induces Assembly of the Pyroptosome and Subsequent Cell Death Cell Viability Assay Oligomerization of ASC

Model of Neuronal Pyroptosis after CND Injury

Summary ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Dr. Juan Pablo de Rivero Vaccari Dr. Gerhard Dahl Dr. W. Dalton Dietrich Acknowledgments Julia Minkiewicz Stephanie Bacik

Keane, Robert

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