Search

The inflammasome is an important innate immune pathway that regulates at least two host responses protective against infections: (1) secretion of the proinflammatory cytokines IL-1β and IL-18 and (2) induction of pyroptosis, a form of cell death. Inflammasomes, of which different types have been identified, are multiprotein complexes containing pattern recognition receptors belonging to the Nod-like receptor family or the PYHIN family and the protease caspase-1. The molecular aspects involved in the activation of different inflammasomes by various pathogens are being rapidly elucidated, and their role during infections is being characterized. Production of IL-1β and IL-18 and induction of pyroptosis of the infected cell have been shown to be protective against many infectious agents. Here, we review the recent literature concerning inflammasome activation in the context of bacterial infections and identify important questions to be answered in the future.

NOD-like receptors (NLRs) constitute a recently identified family of macromolecules that participate in regulation of innate immune responses. To date, 23 members of the NLR family are identified in humans. Diverse NLRs are stimulated by a broad range of pathogen- or danger-associated molecular patterns, and collectively function as intracellular pattern recognition receptors (PRRs). The most studied inflammasomes are NLRP1 and NLRP3 that process inactive pro-caspase-1 to its active form, allowing the cleavage and subsequent activation of pro-IL-1β and pro-IL-18, and initiation of inflammatory responses. Three models, based upon extracellular ATP/K(+) flux, lysosomal release of cathepsin, and reactive oxygen species, have been proposed to be involved in signaling activation of NLRs and downstream events. In this review, I discuss the current state of knowledge related to the roles of NLRs and inflammasomes in the development of cardiovascular diseases.

The metabolic syndrome refers to a well defined group of risk factors, including central obesity and inflammation, for the development of diabetes and cardiovascular disease. Interestingly, many studies have recently led to the emergence of somewhat unexpected relationships between several infectious diseases and various aspects of the metabolic syndrome. Our understanding of the mechanisms underlying these interactions is also rapidly developing and some of these are summarized in this article. We will focus first on bacterial infection, and most notably the role of gut microbiota in regulaton of both obesity and inflammation. In particular, we focus on the role of inflammasomes and propose that understanding the role of Toll-like receptors and Nod-like receptors in the pathogenesis of inflammatory disorders with or without infection may provide novel targets for prevention and/or treatment of associated diseases. Secondly, chronic bacterial or viral infection and emerging links with metabolism will be reviewed. Finally, consideratons of biomarkers for metabolic syndrome, in particular lipocalin-2, and their link with infection will be discussed.