NLRs a Cytosolic Armory of Microbial Sensors Linked to Human Diseases

Mathias Chamaillard

1 Introduction 170

2 NLRs, a Conserved Cytosolic Arm of the Innate Immune System 171

3 Physiological Role of NLRs in Innate and Adaptive Immunity: NLRs Join TLRs 174

3.1 Host Sensing of Non-TLR PAMPs: Lessons from NOD1 and NOD2 Studies 174

3.2 NLRs Promote Maturation of TLR-Induced Il-1 ß and IL-18 Release 176

4 What Can we Learn from NLRs Linked to Human Diseases? 177

4.1 NOD1 and NOD2 Mutations Linked to Chronic Inflammatory Diseases 178

4.2 Auto-Inflammatory Diseases 179

4.3 Reproduction Diseases 179

5 Concluding Remarks: Towards the Development of "Magic" Bullets 179

References 180

Abstract In mammals, a tissue-specific set of Nod-like receptors (NLRs) enables collectively a swift and differential cytosolic detection of evolutionary distant microbial- and/or danger-associated molecular patterns from the extracellular and intracellular microenvironment. Repressing and de-repressing this surveillance machinery contribute to vital immune homeostasis and protective responses within specific tissues. Conversely, defective biology of NLR signaling pathways drives the development of recurrent infectious and/or inflammatory diseases by failing to mount barrier functions, to instruct the adaptive immune response and/or to ignore self and non-self antigens. Better decoding of microbial shedding and immune escape strategies will provide clues for the development of rational therapies striving to cure and prevent common and emerging immunopathologies in humans.

INSERM U795, Physiopathology of Inflammatory Bowel Disease, Swynghedauw Hospital, Rue A. Verhaeghe, 59037 Lille, France, [email protected]

H. Heine (ed.), Innate Immunity of Plants, Animals, and Humans. Nucleic Acids and Molecular Biology 21. © Springer-Verlag Berlin Heidelberg 2008

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