Mouse p202 containing two hemopoietic expression, interferon inducibility, nuclear localization (HIN) domains antagonizes AIM2 inflammasome signaling and potentially modifies lupus susceptibility. We found that only HIN1 of p202 binds double-stranded DNA (dsDNA), while HIN2 forms a homotetramer. Crystal structures of HIN1 revealed that dsDNA is bound on face opposite the site used in AIM2 and I...

The AIM2 inflammasome detects double-stranded DNA in the cytosol and induces caspase-1dependent pyroptosis as well as release of the inflammatory cytokines IL-1β and IL-18. AIM2 is critical for host defense against DNA viruses and bacteria that replicate in the cytosol, such as Francisella novicida. AIM2 activation by F. novicida requires bacteriolysis, yet whether this process is accidental or...

Email: [email protected] Abstract: Understanding the inflammasome biology is one of the most exciting challenges in immuno-pharmacology. The role of the inflammasomes has been recognized in the host defense mechanism against invading pathogens and in the development of several conditions, such as cancer, auto-inflammatory, autoimmune, metabolic and neurodegenerative disorders. DNA recogn...

Detailing the inflammatory mechanisms of biomaterial-implant induced foreign body responses (FBR) has implications for revealing targetable pathways that may reduce leukocyte activation and fibrotic encapsulation of the implant. We have adapted a model of poly(methylmethacrylate) (PMMA) bead injection to perform an assessment of the mechanistic role of the ASC-dependent inflammasome in this pro...

OBJECTIVE SLE is more prevalent in females, but may cause more severe organ damage in males. The underlying mechanism is incompletely understood. Since macrophage plays a key role in SLE pathogenesis, the present work aimed to investigate whether inflammasomes in male and female SLE macrophages are differentially activated. METHODS Macrophages were derived from peripheral blood mononuclear ce...

Listeria monocytogenes invades the cytoplasm of macrophages and induces the activation of caspase-1 and the subsequent maturation of IL-1beta and IL-18. Although apoptosis-associated speck-like protein containing a caspase-activating and recruitment domain (ASC), an adaptor protein of nucleotide-binding oligomerization domain (Nod)-like receptors, has been shown to play an essential role in ind...

Anti-idiotype antibodies have potential therapeutic applications in many fields, including autoimmune diseases. Herein we report the isolation and characterization of AIM2, an anti-idiotype antibody elicited in a mouse model upon expression of the celiac disease-specific autoantibody MB2.8 (directed against the main disease autoantigen type 2 transglutaminase, TG2). To characterize the interact...

Innate immune pattern recognition receptors sense nucleic acids from microbes and orchestrate cytokine production to resolve infection. Inappropriate recognition of host nucleic acids also results in autoimmune disease. In this study, we use a model of inflammation resulting from accrual of self DNA (DNase II(-/-) type I IFN receptor [Ifnar](-/-)) to understand the role of pattern recognition r...

Abstract The epithelium performs a growing list of immunologically relevant functions at mucosal sites. Specialized epithelial cells the intestine interact with microbiota and lamina propria immune to regulate host defense, yet we know little about molecular regulators linking these interactions during different immunological insults. Here, found that DNA sensor Absent in Melanoma 2 (AIM2) prom...