Unsuccessful pathogenic activities may be key to activating host defenses to infection

Kagan and Fitzgerald comprehensively review the functions and mechanisms of Toll-like receptors (TLRs), which are crucial detectors of microbial biomolecules and mediators of cellular immunity. They...

Innate immune pattern recognition receptors (PRRs) emerged early in evolution. It is generally assumed that structurally homologous proteins in distinct species will operate via similar mechanisms....

Defective host defenses later in life are associated with changes in immune system activity. The means to correct immune defects to ensure immunity in the elderly are undefined. In this study, we...

In this interview, immunologist Ruslan Medzhitov explains how fundamental inflammation is, why it often goes wrong, and whether there's anything we can do about chronic inflammation.

Inflammasome activation in dendritic cells (DCs) leads to pyroptosis or hyperactivation. Zhivaki et al. show that in contrast to pyroptotic DCs, hyperactive DCs stimulate durable anti-tumor immunity...

Devant et al. investigate the actions of reactive oxygen species on the pore-forming protein GSDMD. They show that oxidation of a specific cysteine in GSDMD (C192) promotes its oligomerization,...

Eastwood et al. describe a system for export of recombinant proteins in membrane-bound vesicles from E. coli. A simple peptide tag allows high-yield production of functional proteins within vesicle...

Reactive oxygen species (ROS) affect inflammation and immunity in a multitude of ways, in particular in the context of the signaling pathways that determine cell fate. Inflammasomes are multiprotein...

The regulation of self-DNA reactivity of cGAS is evolutionarily diverse in mammals.

Pathogens manipulate the host immune system to induce the wrong effector response known as immune deviation; however, the mechanisms of immune deviation are poorly understood. Agaronyan et al....

Innate immune signaling complexes are multifunctional organizing centers that can be rewired to induce user-defined cellular outcomes.

Bacteria encode gasdermins that are activated by dedicated proteases, defend from phage, and induce cell death.

Nature - The transcription factor NFIL3 acts antagonistically to C/EBP proteins by binding the Zeb2 enhancer to prevent Zeb2 expression and the development of the conventional type 2 dendritic cell...

The cGAS-STING pathway plays a central role in health and disease. In this review, we describe the current understanding of the molecular mechanisms that control the activity of this pathway.

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The findings that a multitude of animals, from coral to mammals, encode cGAS-like signaling proteins, which produce an array of nucleotide second messenger signals, suggest that this family of...

The BORC complex prevents human autoimmune disease by controlling endosomal TLR7 levels.

In order to maintain homeostasis, tissue-resident macrophages surround and hide very small tissue lesions to prevent excess inflammation driven by neutrophils.

Nature Immunology - Neutrophils can release S100A8/S100A9 as an alarmin via gasdermin D pores. Here, the authors untangle the regulatory mechanisms driving this pathway and show that active repair...

Proteins that drive inflammasome activities are responsive to diverse threats to the host, including infection, tissue damage, or both. Upon threat identification, specific regulatory proteins seed...

Thermo Scientific Subcellular Protein Fractionation Kit for Cultured Cells enables segregation and enrichment of proteins from five different cellular compartments.Features of Subcellular Protein...

Key Points. Annotated lncRNA 1810058I24Rik encodes a conserved mitochondrial micropeptide.Macrophages fail to activate the Nlrp3 inflammasome in the absenc

Nature Immunology - Sun and colleagues describe that the secretion of interleukin-33 is dependent on a p40 N-terminal fragment of gasdermin D, whose generation is independent of inflammatory...

Disease-associated mutations in the kinase Lrrk2 promote association of gasdermin D with mitochondrial membranes, which induces release of reactive oxygen species, a switch toward necroptotic cell...

Inflammasomes are critical initiators of inflammation and adaptive immunity with far-reaching effects on human health and disease. This review provides a 360° view of the mechanisms of inflammasome...

Nature Immunology - A dogma in the inflammasome field is that NLRP3 activation occurs at dispersed vesicles of the trans-Golgi network. Here, Ricci and colleagues find that these vesicles are of...

Nature - Cryptococcus neoformans secretes CPL1 protein, which induces alternative activation of macrophages via Toll-like receptor 4 in mice and is essential for fungal virulence.

Nature - N-acetylglucosamine kinase catalyses the phosphorylation of muramyl dipeptide and is thus essential for its recognition and immunostimulatory activity in human and mouse cells.

Author summary Salmonella enterica serovar Typhimurium is a gastrointestinal bacterial pathogen that causes diarrheal disease and is a major cause of morbidity and mortality worldwide. Salmonella...

The process of pyroptosis is mediated by inflammasomes and a downstream effector known as gasdermin D (GSDMD). Upon cleavage by inflammasome-associated caspases, the N-terminal domain of GSDMD forms...

Nature - A study using mouse models of food allergy shows that allergic sensitization drives antigen-specific avoidance behaviour mediated by immunoglobulin E antibodies and mast cells.

Jonathan Kagan named Neutra Professor of Pediatrics

To cause infection, pathogens must overcome bottlenecks imposed by the host immune system. These bottlenecks restrict the inoculum and largely dete...

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Tsuchiya et al. demonstrate that rapid processing and release of IL-1α induced by non-particulate activators of canonical and non-canonical inflammasomes depend on GSDMD. They demonstrate that plasma...

In mammals, cyclic dinucleotides (CDNs) bind and activate STING to initiate an antiviral type I interferon response. CDNs and STING originated in b...