IgE Immune Complexes Mitigate Eosinophilic Immune Responses through NLRC4 Inflammasome.

Immune complexes (ICs) skew immune responses toward either a pro- or anti-inflammatory direction based on the type of stimulation. Immunoglobulin E (IgE) is associated with Th2 immune responses and known to activate innate immune cells. However, roles of antigen (Ag)-specific-IgE ICs in regulating human eosinophil responses remain elusive; therefore, this study builts upon the mechanism of which ovalbumin (Ova)-IgE ICs affects eosinophilic responses utilizing human EoL-1 cell line as a model.

Duality of Valproic Acid Effects on Inflammation, Oxidative Stress and Autophagy in Human Eosinophilic Cells.

Eosinophils function in rapid innate immune responses and allergic reactions. Recent research has raised the possibility that the histone deacetylase inhibitor valproic acid (VPA) may be a promising therapeutic agent for treatment of allergic responses and certain cancers. However, its effects on eosinophils remain unclear.

Computational Modeling of T Cell Hypersensitivity during Coronavirus Infections Leading to Autoimmunity and Lethality.

The human angiotensin-converting enzyme 2 (hACE2) receptor is the primary receptor for SARS-CoV-2 infection. However, the presence of alternative receptors such as the transmembrane glycoprotein CD147 has been proposed as a potential route for SARS-CoV-2 infection. The outcomes of SARS-CoV-2 spike protein binding to receptors have been shown to vary among individuals.

NLRC4 Inflammasome-Mediated Regulation of Eosinophilic Functions.

Eosinophils play critical roles in the maintenance of homeostasis in innate and adaptive immunity. Although primarily known for their roles in parasitic infections and the development of Th2 cell responses, eosinophils also play complex roles in other immune responses ranging from anti-inflammation to defense against viral and bacterial infections. However, the contributions of pattern recognition receptors in general, and NOD-like receptors (NLRs) in particular, to eosinophil involvement in these immune responses remain relatively underappreciated.

Adenosine-Induced NLRP11 in B Lymphoblasts Suppresses Human CD4 T Helper Cell Responses.

NLRP11 is a member of the PYD domain-containing, nucleotide-binding oligomerization-domain (NOD-) like receptor (NLR) family. The true stimulus of NLRP11 is still unclear to date, so the current study is built upon NLRP11 induction via adenosine stimulation and that activation can shape adaptive immune responses in a caspase-1-independent manner. We examined the regulation and mechanism of adenosine responsiveness via NLRP11 in human Daudi Burkitt's B lymphoma cells and their effects on human peripheral CD4 T lymphocytes from healthy individuals.

Immune Complexes Indirectly Suppress the Generation of Th17 Responses In Vivo.

The precise context in which the innate immune system is activated plays a pivotal role in the subsequent instruction of CD4+ T helper (Th) cell responses. Th1 responses are downregulated when antigen is encountered in the presence of antigen-IgG immune complexes. To assess if Th17 responses to antigen are subject to similar influences in the presence of immune complexes we utilized an inflammatory airway disease model in which immunization of mice with Complete Freund's Adjuvant (CFA) and ovalbumin (Ova) induces a powerful Ova-specific Th1 and Th17 response.

Immune complexes inhibit IL-1 secretion and inflammasome activation.

IgG immune complexes have been shown to modify immune responses driven by APCs in either a pro- or anti-inflammatory direction depending upon the context of stimulation. However, the ability of immune complexes to modulate the inflammasome-dependent innate immune response is unknown. In this study, we show that IgG immune complexes suppress IL-1α and IL-1β secretion through inhibition of inflammasome activation.

Control of innate and adaptive immunity by the inflammasome.

The importance of innate immunity lies not only in directly confronting pathogenic and non-pathogenic insults but also in instructing the development of an efficient adaptive immune response. The Nlrp3 inflammasome provides a platform for the activation of caspase-1 with the subsequent processing and secretion of IL-1 family members. Given the importance of IL-1 in a variety of inflammatory diseases, understanding the role of the Nlrp3 inflammasome in the initiation of innate and adaptive immune responses cannot be overstated.

NLRC5 knockdown in chicken macrophages alters response to LPS and poly (I:C) stimulation.

Background: NLRC5 is a member of the CARD domain containing, nucleotide-binding oligomerization (NOD)-like receptor (NLR) family, which recognizes pathogen-associated molecular patterns (PAMPs) and initiates an innate immune response leading to inflammation and/or cell death. However, the specific role of NLRC5 as a modulator of the inflammatory immune response remains controversial. It has been reported to be a mediator of type I IFNs, NF-kB, and MHC class I gene.

Inhibitors of apoptosis proteins and IL-1β: a tangled relationship.

Inhibitors of apoptosis proteins (IAPs) are important regulators of both cell death and inflammation. In this issue of Immunity, Vince et al. (2012) report that inhibition of IAPs results in the processing and secretion of IL-1β through RIP3-mediated caspase-1- and caspase-8-dependent pathways.

Avian-specific TLRs and downstream effector responses to CpG-induction in chicken macrophages.

Chickens possess toll-like receptor (TLR15), a pattern recognition receptor (PRR) absent in mammals. We characterized the regulation and mechanism of CpG responsiveness via TLRs in chicken macrophage HD11 cells. TLR15 was significantly upregulated after induction with B- and C-type CpG oligonucleotides (ODN), tripalmitoylated lipopeptide (PAM3CSK4), Escherichia coli- and Salmonella enteritidis-derived lipopolysaccharide (LPS).

Unique genome-wide transcriptome profiles of chicken macrophages exposed to Salmonella-derived endotoxin.

Background: Macrophages play essential roles in both innate and adaptive immune responses. Bacteria require endotoxin, a complex lipopolysaccharide, for outer membrane permeability and the host interprets endotoxin as a signal to initiate an innate immune response. The focus of this study is kinetic and global transcriptional analysis of the chicken macrophage response to in vitro stimulation with endotoxin from Salmonella typhimurium-798.

Immunization with UV-induced apoptotic cells generates monoclonal antibodies against proteins differentially expressed in hepatocellular carcinoma cell lines.

Early and differential diagnosis of hepatocellular carcinoma (HCC) requires sensitive and specific tissue and serum markers. On the other hand, proteins involved in tumorigenesis are extensively modulated on exposure to apoptotic stimuli, including ultraviolet (UVC) irradiation. Hence, we generated monoclonal antibodies by using UVC-irradiated apoptotic cells of an HCC cell line, HUH7, aiming to explore proteins differentially expressed in tumors and apoptosis.

Breed effect on early cytokine mRNA expression in spleen and cecum of chickens with and without Salmonella enteritidis infection.

We examined mRNA expression of 11 genes: BAK, Bcl-x, Interferon [IFN]-gamma, Interleukin [IL]-1beta, IL-6, IL-10, IL-12alpha, IL-12beta, IL-18, CXCLi2 [IL-8/CAF], and a MIP family chemokine, CCLi2, in the spleen and cecum of day-old chicks after oral inoculation with Salmonella enteritidis (SE) or medium. Three distinct chicken breeds (broiler, Fayoumi, and Leghorn) were evaluated for mRNA expression levels at 2 and 18h post-inoculation using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). SE exposure significantly increased splenic IL-18 and IFN-gamma expression.