Trends in immunology
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Trends in immunology · Jan 2012
ReviewParticipation of blood vessel cells in human adaptive immune responses.
Circulating T cells contact blood vessels either when they extravasate across the walls of microvessels into inflamed tissues or when they enter into the walls of larger vessels in inflammatory diseases such as atherosclerosis. The blood vessel wall is largely composed of three cell types: endothelial cells lining the entire vascular tree; pericytes supporting the endothelium of microvessels; and smooth muscle cells forming the bulk of large vessel walls. Each of these cell types interacts with and alters the behavior of infiltrating T cells in different ways, making these cells active participants in the processes of immune-mediated inflammation. In this review, we compare and contrast what is known about the nature of these interactions in humans.
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Trends in immunology · Jul 2011
ReviewHistone deacetylases as regulators of inflammation and immunity.
Histone deacetylases (HDACs) remove an acetyl group from lysine residues of target proteins to regulate cellular processes. Small-molecule inhibitors of HDACs cause cellular growth arrest, differentiation and/or apoptosis, and some are used clinically as anticancer drugs. In animal models, HDAC inhibitors are therapeutic for several inflammatory diseases, but exacerbate atherosclerosis and compromise host defence. ⋯ These contrasting effects might reflect distinct roles for individual HDACs in immune responses. Here, we review the current understanding of innate and adaptive immune pathways that are regulated by classical HDAC enzymes. The objective is to provide a rationale for targeting (or not targeting) individual HDAC enzymes with inhibitors for future immune-related applications.
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Trends in immunology · Mar 2011
ReviewInflammasome activation and IL-1β and IL-18 processing during infection.
Interleukin-1β (IL-1β) and IL-18 contribute to host defense against infection by augmenting antimicrobial properties of phagocytes and initiating Th1 and Th17 adaptive immune responses. Protein complexes called inflammasomes activate intracellular caspase-1 autocatalytically, which cleaves the inactive precursors of IL-1β and IL-18 into bioactive cytokines. In this review, we discuss the controversies regarding inflammasome activation and the role of the inflammasome during infection. We highlight alternative mechanisms for processing IL-1β and IL-18 during infection, which involve extracellular cleavage of the inactive cytokines by neutrophil-derived serine proteases or proteases released from cytotoxic T cells.
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Trends in immunology · Oct 2009
ReviewEndotoxin tolerance: new mechanisms, molecules and clinical significance.
Prior exposure of innate immune cells like monocytes/macrophages to minute amounts of endotoxin cause them to become refractory to subsequent endotoxin challenge, a phenomenon called "endotoxin tolerance". Clinically, this state is associated with monocytes/macrophages in sepsis patients where they contribute to "immunosuppression" and mortality. ⋯ The recent appreciation of inflammation as a self-regulating process, the relative contribution of MyD88 versus TRIF signaling pathways in inducing activation or tolerance, plasticity of NF-kappaB function and the role of chromatin modification and microRNAs in LPS-induced gene reprogramming urges a re-evaluation of endotoxin tolerance. This review integrates these new findings into an up-to-date account of endotoxin tolerance, its molecular basis and clinical implications in different pathologies.
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Staphylococcus aureus is a versatile and harmful pathogen in both hospital- and community-associated infections that range from superficial to systemic infections. S. aureus engages a multitude of mechanisms to subvert the innate immune response of the host, including inhibition of complement activation and neutralization of anti-microbial peptides. ⋯ Recent and rapidly growing experimental evidence indicates the existence of a machinery of anti-adhesive and anti-chemotactic moieties of S. aureus that allow the bacterium to interfere with specific adhesive steps of the homing mechanism of leukocytes. Understanding the functions of these S. aureus-derived anti-inflammatory agents could also provide the platform for designing new therapies in several inflammatory and autoimmune diseases.