The inflammasomes: guardians of the body.

The innate immune system relies on its capacity to rapidly detect invading pathogenic microbes as foreign and to eliminate them. The discovery of Toll-like receptors (TLRs) provided a class of membrane receptors that sense extracellular microbes and trigger antipathogen signaling cascades. More recently, intracellular microbial sensors have been identified, including NOD-like receptors (NLRs). Some of the NLRs also sense nonmicrobial danger signals and form large cytoplasmic complexes called inflammasomes that link the sensing of microbial products and metabolic stress to the proteolytic activation of the proinflammatory cytokines IL-1beta and IL-18. The NALP3 inflammasome has been associated with several autoinflammatory conditions including gout. Likewise, the NALP3 inflammasome is a crucial element in the adjuvant effect of aluminum and can direct a humoral adaptive immune response. In this review, we discuss the role of NLRs, and in particular the inflammasomes, in the recognition of microbial and danger components and the role they play in health and disease.

Innate immune recognition of nucleic acids.

The innate immune system employs a number of pattern recognition receptor families in response to DNAs and RNAs, either from invading microbes or within the hosts. These include the Toll-like receptors (TLRs), the retinoic acid inducible gene I (RIG-I) like receptors (RLRs), and the nucleotide-binding domain leucine-rich repeat/NOD-like receptor (NLRs), among other potential sensors in the cytoplasm. These receptors are composed of modular domain architecture, with ligand binding/sensing domains and signaling domains regulated either through dimerization/oligomerization, or conformational changes directed by enzymatic activities. Signaling pathways from different families of receptors converge on their respective common adapter proteins and lead to activation of transcription factors or caspases. Many of these receptors induce orchestrated responses to similar ligands from different cell types, resulting in redundant and complementary immunity to infections. This highly efficient defense system is a double-edged sword: inappropriate reaction to host ligands leads to compromised innate tolerance and autoimmune diseases. Structural studies of innate immune receptors and their signaling pathways are essential in our understanding of pattern recognition mechanisms and design of more efficient vaccine adjuvants.