NLRC4 Inflammasome Research Articles

Elevated expression of the AIM2 gene in response to Helicobacter pylori along with the decrease of NLRC4 inflammasome is associated with peptic ulcer development.

Helicobacter Pylori (H. Pylori) cause peptic ulcer disease (PUD), but the inflammasome's role in PUD is not well understood. Therefore this study has investigated inflammasome compartment expression and IL-1β production in gastritis (G) and peptic ulcer disease. This study was based on gene expression of inflammasome compartments on stomach biopsies of 50 patients with PUD as cases and 50 individuals with gastritis as controls. The expression of NLRC4, ASC, IL-18, and serum IL-1β decreased in the PUD group compared to the control group. AIM2 gene expression increased, and NLRP12 gene expression decreased in H. pylori-seropositive positive (HP+ ) individuals compared to H. pylori-seronegative (HP- ) individuals. The G-HP+ subjects had higher serum IL-1β and AIM2 gene expression than G-HP- subjects but lower NLRP3 and NLRP12 gene expression. The PUD-HP+ had lower serum IL-1β, but higher AIM2 and IL-18 expression than PUD-HP- . The PUD-HP- patients had decreased IL-18 expression than G-HP- group. The PUD-HP+ had lower serum IL-1β and NLRC4 expression than G-HP+, while NLRP1 and NLRP3 were higher in expression in PUD-HP+ . The expression of caspase-1, NLRP3 and NAIP were correlated with IL-1β and IL-18. In conclusion, a decrease in NLRC4, IL-18, ASC genes, and IL-1β levels in PUD patients compared to gastritis may act in the development of PUD. H. pylori caused AIM2 induction and reduced NLRP12, indicating their contribution to bacterial responses. Decreased NLRC4 expression and IL-1β protein, together with enhanced NLRP1, and NLRP3 expression, promotes H. pylori to develop peptic ulcers.

Inhibition of LRRK2 Kinase Activity with a Novel Inhibitor (CS 82) Inhibits NLRC4 Inflammasome Activation and Reduces Intestinal Inflammation Severity

Abstract In the last twenty years Leucine Rich Repeat Kinase 2 (LRRK2) has received immense attention due to its association with several diseases, for example, neurodegenerative disease PD (Parkinson’s Disease), inflammatory bowel disease (IBD), Crohn’s disease (CD), infectious disease Leprosy etc. Not only do genetic mutations make this protein a hotspot for various diseases but also it shows some pleotropic characteristics which might influence several diseases. LRRK2 directly controls several proteins for example Rab GTPase proteins, NLRC4 inflammasomes etc. NLRC4 also showed correlation with auto-inflammatory diseases such as CD, Macrophage Activation Syndrome (MAS) etc. Here we report that NLRC4 dependent cytokine storm retarded through LRRK2 kinase inhibition as well as reduces severity of intestinal inflammation. For LRRK2 kinase inhibition a novel kinase inhibitor (Termed CS 82) has been used. In vitro studies disclosed that this inhibitor suppress LRRK2 phosphorylation as well as its ability to phosphorylate the LRRK2 targets, Rab 10 and 12; in addition, they suppress human dendritic cell production of TNFa stimulated by several known LRRK2 activators including the Dectin-1-ligand, zymosan- depleted S. cerevisiae extract. Finally, the inhibitors exhibited powerful suppression of the ability of LRRK2 to mediate NLRC4 inflammasome production of IL-1beta. LRRK2 deficiency showed inhibitor has no effect on NLRC4 dependent IL-1b cytokine productions. These findings suggest that inhibition of LRRK2 kinase activity retarded NLRC4 inflammasome activation which reduces IL-1b cytokine productions and intestinal inflammation severity.

An animal model for autoinflammation with infantile enterocolitis

Abstract Autoinflammation with infantile enterocolitis (AIFEC) is one of the emerging life-threatening diseases caused by inborn errors of NLRC4 inflammasome. The pathogenicity of AIFEC remains largely unknown and standard therapy is lacking due to rare patient cases and high mortality. To fill the gap, it is urgent to set up an effective animal model for this rare disease. We have recently generated a loxP-flanked NLRC4 V341A conditional knock-in (KI) mouse line where human V341A (GTG to GCG) mutation was introduced into the corresponding mouse Nlrc4coding sequence. When this line is bred with distinct Cre transgenic mice, the KI allele can be expressed globally or cell-type specifically. We bred the KI line with E2a-Cre transgenic mice and got globally expressed V341A KI mice, and the KI mice developed autoinflammation with infantile enterocolitis that recapitulated the symptoms of AIFEC patients. In brief, immunoblot demonstrated KI mice had hyperactivation of NLRC4 inflammasome in gut epithelium and macrophages. The neonatal KI pups had significant intestinal inflammation, accompanied with diarrheal, impaired barrier integrity and dysbiosis. Furthermore, the KI pups had dramatically elevated IL-1β, IL-6 and IL-18 in sera and supernatant of colon explant cultures. Meanwhile, the KI pups exhibited cytopenia, hemophagocytosis, and macrophage hyperactivation. Biochemical assays suggested multi-organ damage in KI mice, including the liver, kidney, and heart, accompanied with hyper serum ferritin level. Without any intervention, the pups died before day 10 postnatally. Taken together, we have established a novel animal model for AIFEC, thus providing a platform to elucidate the pathogenesis of AIFEC and test therapeutic strategies. Startup fund from the Department of pathology at the University of IOWA, NIH R21AG076895, R01 NS104164

A new acid isolated from V. negundo L. inhibits NLRP3 inflammasome activation and protects against inflammatory diseases.

The NLRP3 inflammasome plays a critical role in the innate immune response, and its excessive activation will cause pyroptotic cell death and be associated with the onset of inflammatory diseases. However, NLRP3 inflammasome targeting therapies are still to be implemented in the clinic setting. Here, we first isolated, purified and characterized a novel Vitenegu acid from V. negundo L. herb that specifically inhibits NLRP3 inflammasome activation, without affecting NLRC4 or AIM2 inflammasomes. Vitenegu acid blocks the oligomerization of NLRP3, thus inhibiting NLRP3 inflammasome assembly and activation. In vivo data show that Vitenegu acid exerts therapeutic effects on NLRP3 inflammasome-dependent inflammation. Taken together, our results suggest that Vitenegu acid is a candidate therapeutic agent for treating NLRP3 inflammasome related diseases.

TRIM29 (Tripartite Motif Containing 29) Alleviates NLRC4 (NLR Family CARD Domain Containing Protein 4) Inflammasome Related Cerebral Injury via Promoting Proteasomal Degradation of NLRC4 in Ischemic Stroke

Neuroinflammation plays extremely crucial roles in the neurological damage mediated by ischemic stroke. TRIM29 (tripartite motif containing 29) has previously been proposed to contribute to the regulation of innate immunity, however, the effect of TRIM29 on ischemic stroke induced neurodegenerative processes and neuroinflammation still largely unexplored. In the current article, we aimed to investigate the function and the precise mechanisms of TRIM29 in ischemic stroke. Middle cerebral artery occlusion mice model and oxygen-glucose deprivation cell model were established as in vivo and in vitro models of ischemic stroke. Quantitative real-time polymerase chain reaction (PCR), Western blot, and ELSIA were used to detect the expression levels of TRIM29, cytokines, and marker proteins. Immunofluorescence assay was performed to examine the extent of cell death. Different truncations were generated, and coimmunoprecipitation assays were used to confirm the protein interaction. Ubiquitination assay was performed to detect the ubiquitination levels. We found that the cerebral ischemia-reperfusion induced injury was aggravated in TRIM29 knockout mice after middle cerebral artery occlusion operation as well as the increased neurological deficits score. TRIM29 expression was also found to be up-regulated upon middle cerebral artery occlusion or OGD administration, and loss of TRIM29 promoted the apoptosis and pyroptosis of neurons and microglial cells induced by middle cerebral artery occlusion or OGD, consistent with the enhanced proinflammatory mediators production and activation of NLRC4 (NLR [NOD-like receptor] family CARD [caspase recruitment domain] domain containing protein 4) inflammasome. Furthermore, we observed that TRIM29 interacted with NLRC4 directly and promoted the K48-linked polyubiquitination of NLRC4, lead to the proteasomal degradation of NLRC4. In conclusion, for the first time, we revealed the role of TRIM29 in ischemic stroke and illustrated the direct relationship between TRIM29 and NLRC4.

Novel Aryl Sulfonamide Derivatives as NLRP3 Inflammasome Inhibitors for the Potential Treatment of Cancer.

The NLRP3 inflammasome is a critical component of innate immunity that senses diverse pathogen- and host-derived molecules. However, its aberrant activation has been associated with the pathogenesis of multiple diseases, including cancer. In this study, we designed and synthesized a series of aryl sulfonamide derivatives (ASDs) to inhibit the NLRP3 inflammasome. Among these, compounds 6c, 7n, and 10 specifically inhibited NLRP3 activation at nanomolar concentrations without affecting the activation of the NLRC4 and AIM2 inflammasomes. Furthermore, we demonstrated that these compounds reduce interleukin-1β (IL-1β) production in vivo and attenuate melanoma tumor growth. Moreover, metabolic stability in liver microsomes of 6c, 7n, and 10 was studied along with plasma exposure in mice of the most interesting compound 6c. Therefore, we generated potent NLRP3 inflammasome inhibitors, which can be considered in future medicinal chemistry and pharmacological studies aimed at developing a new therapeutic approach for NLRP3 inflammasome-driven cancer.

Ribosome-rescuer PELO catalyzes the oligomeric assembly of NOD-like receptor family proteins via activating their ATPase enzymatic activity

NOD-like receptors (NLRs) are pattern recognition receptors for diverse innate immune responses. Self-oligomerization after engagement with a ligand is a generally accepted model for the activation of each NLR. We report here that a catalyzer was required for NLR self-oligomerization. PELO, a well-known surveillance factor in translational quality control and/or ribosome rescue, interacted with all cytosolic NLRs and activated their ATPase activity. In the case of flagellin-initiated NLRC4 inflammasome activation, flagellin-bound NAIP5 recruited the first NLRC4 and then PELO was required for correctly assembling the rest of NLRC4s into the NLRC4 complex, one by one, by activating the NLRC4 ATPase activity. Stoichiometric and functional data revealed that PELO was not a structural constituent of the NLRC4 inflammasome but a powerful catalyzer for its assembly. The catalytic role of PELO in the activation of cytosolic NLRs provides insight into NLR activation and provides a direction for future studies of NLR family members.

Cornus officinalis Seed Extract Inhibits AIM2-Inflammasome Activation and Attenuates Imiquimod-Induced Psoriasis-like Skin Inflammation

The AIM2 inflammasome is an innate immune system component that defends against cytosolic bacteria and DNA viruses, but its aberrant activation can lead to the progression of various inflammatory diseases, including psoriasis. However, there have been few reports of specific inhibitors of AIM2 inflammasome activation. In this study, we aimed to investigate the inhibitory activity of ethanolic extracts of seeds of Cornus officinalis (CO), a herb and food plant used in traditional medicine, on AIM2-inflammasome activation. We found that CO inhibited the release of IL-1β induced by dsDNA in both BMDMs and HaCaT cells, but that it showed no effect on the release of IL-1β induced by NLRP3 inflammasome triggers, such as nigericin and silica, or the NLRC4 inflammasome trigger flagellin. Furthermore, we demonstrated that CO inhibited the cleavage of caspase-1, an inflammasome activation marker, and an upstream event, the translocation and speck formation of ASC. In addition, further experiments and mechanistic investigations revealed that CO can inhibit AIM2 speck formation induced by dsDNA in AIM2-overexpressing HEK293T cells. To verify the correlation in vivo, we investigated the efficacy of CO in an imiquimod (IMQ)-induced psoriasis model, which has reported associations with the AIM2 inflammasome. We found that topical application of CO alleviated psoriasis-like symptoms, such as erythema, scaling, and epidermal thickening, in a dose-dependent manner. Moreover, CO also significantly decreased IMQ-induced expression of AIM2 inflammasome components, including AIM2, ASC, and caspase-1, and led to the elevation of serum IL-17A. In conclusion, our results suggest that CO may be a valuable candidate for the discovery of AIM2 inhibitors and the regulation of AIM2-related diseases.

Non-canonical NLRC4 inflammasomes in astrocytes contribute to glioma malignancy.

The present study was designed to explore the pathological role of non-canonical NLRC4 inflammasome in glioma. This retrospective study included bioinformatical analysis, including survival, gene ontology, ssGSEA, cox regression, IPA and drug repositioning with TCGA and DepMap database. Experimental validations were conducted in glioma patient's sample and evaluated with histological or cellular functional analysis. Clinical dataset analysis revealed that non-canonical NLRC4 inflammasomes significantly contribute to glioma progression and poor survival rates. Experimental validation was revealed that the expression of non-canonical NLRC4 inflammasomes were co-localized with astrocytes in malignant gliomas, with a sustained clinical correlation observed between astrocytes and inflammasome signatures. Indeed, the formation of an inflammatory microenvironment increased in malignant gliomas, leading to pyroptosis, known as inflammatory cell death. Molecular interaction analysis revealed that NF-κB pathways potentially serve as the connecting point between the canonical and noncanonical pathways of the NLRC4 inflammasome. Finally, drug repositioning analysis of non-canonical NLRC4 inflammasome-associated molecules revealed that MK-5108, PF4981517, and CTEP may represent effective options for glioma therapy. The findings of this study suggest that non-canonical NLRC4 inflammasomes contribute to poor prognosis in patients with glioma and induce an inflammatory microenvironment. We propose the pathological phenomenon of non-canonical NLRC4 inflammasomes and several therapeutic strategies based on the modulation of the inflammatory tumor microenvironment.

Chronic activation of inflammasome signaling complexes and enhancement of behavioral abnormalities

IntroductionInflammasomes are cytosolic multi-component signaling platforms critical to the innate immune response to infectious diseases and the dysregulation of their activation can lead to the development of neurodegeneration and cancer.ObjectivesWe aim through this review to ass a possible interplay between dysregulation of inflammasome activation, development of chronic inflammatory disease and enhancement of behavioral abnormalities.MethodsWe comprehensively review the scientific literature using Pubmed database and other search platforms such as Google scholar to assess the role and the actors of chronic activation of inflammasome signaling complexes to establish a potential association between dysregulation of inflammasome activation, chronic inflammatory disease and enhancement of behavioral abnormalities.ResultsOur bibliographic review revealed that dysregulation of the inflammasome is associated with the onset and progression of several autoinflammatory and autoimmune diseases, including cryopyrin-associated periodic fever syndrome, familial Mediterranean fever, rheumatoid arthritis, and systemic lupus erythematosus. These multimeric complexes form in response to molecular patterns unique to pathogens and cellular damage, triggering a cascade of downstream responses, including the induction of pyroptotic cell death and release of proinflammatory cytokines. Some inflammasomes directly recognize these patterns, while others indirectly sense these patterns through changes in the homeostatic environment of the cell. Moreover, although being a normal part of the skin flora, yeasts of the genus Malassezia are associated with several inflammatory skin diseases including pityriasis versicolor (tinea versicolor), atopic eczema, psoriasis, Malassezia folliculitis and onychomycoses. In the context of tolerating fungi during colonization and eliciting, activation, of inflammasomes signaling complexes, has been identified as an integral part of antifungal host defense. While the activation of inflammasomes mainly the NLRP3 one, was shown to be pivotal for innate immunity against pathogenic fungi such as candida albicans, their role in the fungal genus Malassezia remains imprecise. Even though, many observations suggest that simultaneous activation of NLRP3, NLRC4 and AIM2 inflammasomes may play an important role.ConclusionsWhereas, chronic inflammasome activation such as by chronic infectious has been tied to the development of metabolic syndromes, neurodegenerative diseases, and cancer progression, a possible interplay between chronic invasion by the genus Malassezia, vigorous immune response to eliminate invading fungal pathogens, disruption of immune sensors of genotoxic stress, development of chronic inflammatory disease and behavioral abnormalities may be a new field of scientific researches.Disclosure of InterestNone Declared

10,11-Dehydrocurvularin attenuates inflammation by suppressing NLRP3 inflammasome activation

10,11-Dehydrocurvularin (DCV) is a natural-product macrolide that has been shown to exert anti-inflammatory activity. However, the underlying mechanism of its anti-inflammatory activity remains poorly understood. Aberrant activation of the NLRP3 inflammasome is involved in diverse inflammation-related diseases, which should be controlled. The results showed that DCV specifically inhibited the activation of the NLRP3 inflammasome in association with reduced IL-1β secretion and caspase-1 activation, without effect on the NLRC4 and AIM2 inflammasomes. Furthermore, DCV disturbed the interaction between NEK7 and NLRP3, resulting in the inhibition of NLRP3 inflammasome activation. The C=C double bond of DCV was required for the NLRP3 inflammasome inhibition induced by DCV. Importantly, DCV ameliorated inflammation in vivo through inhibiting the NLRP3 inflammasome. Taken together, our study reveals a novel mechanism by which DCV suppresses inflammation, which indicates the potential role of DCV in NLRP3 inflammasome-driven inflammatory disorders.

Lethal Caspase-1/4-Dependent Injury Occurs in the First Minutes of Coronary Reperfusion and Requires Calpain Activity.

To study the relationship between caspase-1/4 and reperfusion injury, we measured infarct size (IS) in isolated mouse hearts undergoing 50 min global ischemia/2 h reperfusion. Starting VRT-043198 (VRT) at reperfusion halved IS. The pan-caspase inhibitor emricasan duplicated VRT's protection. IS in caspase-1/4-knockout hearts was similarly reduced, supporting the hypothesis that caspase-1/4 was VRT's only protective target. NLRC4 inflammasomes activate caspase-1. NLRC4 knockout hearts were not protected, eliminating NLRC4 as caspase-1/4's activator. The amount of protection that could be achieved by only suppressing caspase-1/4 activity was limited. In wild-type (WT) hearts, ischemic preconditioning (IPC) was as protective as caspase-1/4 inhibitors. Combining IPC and emricasan in these hearts or preconditioning caspase-1/4-knockout hearts produced an additive IS reduction, indicating that more protection could be achieved by combining treatments. We determined when caspase-1/4 exerted its lethal injury. Starting VRT after 10 min of reperfusion in WT hearts was no longer protective, revealing that caspase-1/4 inflicted its injury within the first 10 min of reperfusion. Ca++ influx at reperfusion might activate caspase-1/4. We tested whether Ca++-dependent soluble adenylyl cyclase (AC10) could be responsible. However, IS in AC10-/- hearts was not different from that in WT control hearts. Ca++-activated calpain has been implicated in reperfusion injury. Calpain could be releasing actin-bound procaspase-1 in cardiomyocytes, which would explain why caspase-1/4-related injury is confined to early reperfusion. The calpain inhibitor calpeptin duplicated emricasan's protection. Unlike IPC, adding calpain to emricasan offered no additional protection, suggesting that caspase-1/4 and calpain may share the same protective target.

Tivantinib alleviates inflammatory diseases by directly targeting NLRP3

NLRP3 inflammasome-mediated immune responses are involved in the pathogenesis of multiple inflammatory diseases, but few clinical drugs are identified that directly target the NLRP3 inflammasome to treat these diseases to date. Here, we show that the anticancer agent tivantinib is a selective inhibitor of NLRP3 and has a strong therapeutic effect on inflammasome-driven disease. Tivantinib specifically inhibits canonical and non-canonical NLRP3 inflammasome activation without affecting AIM2 and NLRC4 inflammasome activation. Mechanistically, Tivantinib inhibits NLRP3 inflammasome by directly blocking NLRP3 ATPase activity and subsequent inflammasome complex assembly. Invivo, Tivantinib reduces IL-1β production in mouse models of lipopolysaccharide (LPS)-induced systemic inflammation, monosodium urate (MSU)-induced peritonitis and Con A-induced acute liver injury (ALI), and also has remarkable preventive and therapeutic effects on experimental autoimmune encephalomyelitis (EAE). In conclusion, our study identifies the anticancer drug tivantinib as a specific inhibitor of NLRP3 and provides a promising therapeutic agent for inflammasome-driven disease.

Author Correction: Mechanism of NAIP—NLRC4 inflammasome activation revealed by cryo-EM structure of unliganded NAIP5

Author Correction: Mechanism of NAIP—NLRC4 inflammasome activation revealed by cryo-EM structure of unliganded NAIP5

Inflammasome activation by Gram-positive bacteria: Mechanisms of activation and regulation.

The inflammasomes are intracellular multimeric protein complexes consisting of an innate immune sensor, the adapter protein ASC and the inflammatory caspases-1 and/or -11 and are important for the host defense against pathogens. Activaton of the receptor leads to formation of the inflammasomes and subsequent processing and activation of caspase-1 that cleaves the proinflammatory cytokines IL-1β and IL-18. Active caspase-1, and in some instances caspase-11, cleaves gasdermin D that translocates to the cell membrane where it forms pores resulting in the cell death program called pyroptosis. Inflammasomes can detect a range of microbial ligands through direct interaction or indirectly through diverse cellular processes including changes in ion fluxes, production of reactive oxygen species and disruption of various host cell functions. In this review, we will focus on the NLRP3, NLRP6, NLRC4 and AIM2 inflammasomes and how they are activated and regulated during infections with Gram-positive bacteria, including Staphylococcus spp., Streptococcus spp. and Listeria monocytogenes.

A hierarchy of cell death pathways confers layered resistance to shigellosis in mice.

Bacteria of the genus Shigella cause shigellosis, a severe gastrointestinal disease driven by bacterial colonization of colonic intestinal epithelial cells. Vertebrates have evolved programmed cell death pathways that sense invasive enteric pathogens and eliminate their intracellular niche. Previously we reported that genetic removal of one such pathway, the NAIP-NLRC4 inflammasome, is sufficient to convert mice from resistant to susceptible to oral Shigella flexneri challenge (Mitchell et al., 2020). Here, we investigate the protective role of additional cell death pathways during oral mouse Shigella infection. We find that the Caspase-11 inflammasome, which senses Shigella LPS, restricts Shigella colonization of the intestinal epithelium in the absence of NAIP-NLRC4. However, this protection is limited when Shigella expresses OspC3, an effector that antagonizes Caspase-11 activity. TNFα, a cytokine that activates Caspase-8-dependent apoptosis, also provides potent protection from Shigella colonization of the intestinal epithelium when mice lack both NAIP-NLRC4 and Caspase-11. The combined genetic removal of Caspases-1, -11, and -8 renders mice hyper-susceptible to oral Shigella infection. Our findings uncover a layered hierarchy of cell death pathways that limit the ability of an invasive gastrointestinal pathogen to cause disease.

Phenolic and quinone methide nor-triterpenes as selective NLRP3 inflammasome inhibitors

Dysregulated inflammasome activity, particularly of the NLRP3 inflammasome, is associated with the development of several inflammatory diseases. The study of molecules directly targeting NLRP3 is an emerging field in the discovery of new therapeutic compounds for the treatment of inflammatory disorders. Friedelane triterpenes are biologically active phytochemicals having a wide range of activities including anti-inflammatory effects. In this work, we evaluated the potential anti-inflammatory activity of phenolic and quinonemethide nor-triterpenes (1–11) isolated from Maytenus retusa and some semisynthetic derivatives (12–16) through inhibition of the NLRP3 inflammasome in macrophages. Among them, we found that triterpenes 6 and 14 were the most potent, showing markedly reduced caspase-1 activity, IL-1β secretion (IC50 = 1.15 µM and 0.19 µM, respectively), and pyroptosis (IC50 = 2.21 µM and 0.13 µM, respectively). Further characterization confirmed their selective inhibition of NLRP3 inflammasome in both canonical and non-canonical activation pathways with no effects on AIM2 or NLRC4 inflammasome activation.

Quantifying Cell Death Induced by the NLRC4 Inflammasome.

The Nod-like Receptor (NLR) apoptosis inhibitory proteins (NAIPs) are cytosolic receptors that sense cytosolic bacterial proteins. NAIP ligation induces its association with NLRC4, leading to the assembly of the NAIP/NLRC4 inflammasome, which induces the activation of the caspase-1 protease. Caspase-1 then cleaves pro-interleukin (IL)-1β, pro-IL-18, and gasdermin D and induces a form of pro-inflammatory cell death, pyroptosis. These processes culminate in host defense against bacterial infection. Here we describe methods for activating NAIP/NLRC4 inflammasome signalling in human and murine macrophages and quantifying inflammasome-induced cell death.

Examining the Kinetics of Phagocytosis-Coupled Inflammasome Activation in Murine Bone Marrow-Derived Dendritic Cells.

In the present chapter, we describe procedures to assess NLRP3 and NLRC4 inflammasome assembly by immunofluorescence microscopy or live cell imaging, together with inflammasome activation by biochemical and immunological techniques upon phagocytosis. We also include a step-by-step guide to automating the counting of inflammasome "specks" after imaging. While our focus resides on murine bone marrow-derived dendritic cells differentiated in the presence of granulocyte-macrophage colony-stimulating factor, which results in a cell population that resembles inflammatory dendritic cells, the strategies described herein may apply to other phagocytes as well.

Expression of NLRC4 Inflammasome and Its Correlation with Treponema denticola in Stage III/IV Periodontitis with Type II Diabetes Mellitus

Expression of NLRC4 Inflammasome and Its Correlation with Treponema denticola in Stage III/IV Periodontitis with Type II Diabetes Mellitus