Non-canonical NLRP3 inflammasome activation and IL-1β signaling are necessary to L. amazonensis control mediated by P2X7 receptor and leukotriene B4.

08:00 EDT 24th June 2019 | BioPortfolio

Summary of "Non-canonical NLRP3 inflammasome activation and IL-1β signaling are necessary to L. amazonensis control mediated by P2X7 receptor and leukotriene B4."

Leishmaniasis is a neglected tropical disease affecting millions of individuals worldwide. P2X7 receptor has been linked to the elimination of Leishmania amazonensis. Biological responses evoked by P2X7 receptor activation have been well-documented, including apoptosis, phagocytosis, cytokine release, such as IL-1β. It was demonstrated that NLRP3 inflammasome activation and IL-1β signaling participated in resistance against L. amazonensis. Furthermore, our group has shown that L. amazonensis elimination through P2X7 receptor activation depended on leukotriene B4 (LTB4) production and release. Therefore, we investigated whether L. amazonensis elimination by P2X7 receptor and LTB4 involved NLRP3 inflammasome activation and IL-1β signaling. We showed that macrophages from NLRP3-/-, ASC-/-, Casp-1/11-/-, gp91phox-/- , and IL-1R-/- mice treated with ATP or LTB4 did not decrease parasitic load as was observed in WT mice. When ASC-/- macrophages were treated with exogenous IL-1β, parasite killing was noted, however, we did not see parasitic load reduction in IL-1R-/- macrophages. Similarly, macrophages from P2X7 receptor-deficient mice treated with IL-1β also showed decreased parasitic load. In addition, when we infected Casp-11-/- macrophages, neither ATP nor LTB4 were able to reduce parasitic load, and Casp-11-/- mice were more susceptible to L. amazonensis infection than were WT mice. Furthermore, P2X7-/- L. amazonensis-infected mice locally treated with exogenous LTB4 showed resistance to infection, characterized by lower parasite load and smaller lesions compared to untreated P2X7-/- mice. A similar observation was noted when infected P2X7-/- mice were treated with IL-1β, i.e., lower parasite load and smaller lesions compared to P2X7-/- mice. These data suggested that L. amazonensis elimination mediated by P2X7 receptor and LTB4 was dependent on non-canonical NLRP3 inflammasome activation, ROS production, and IL-1β signaling.


Journal Details

This article was published in the following journal.

Name: PLoS pathogens
ISSN: 1553-7374
Pages: e1007887


DeepDyve research library

PubMed Articles [17613 Associated PubMed Articles listed on BioPortfolio]

Macrophage priming is dispensable for NLRP3 inflammasome activation and restriction of Leishmania amazonensis replication.

The NLRP3 inflammasome is activated in response to multiple stimuli and triggers activation of caspase-1 (CASP1), IL-1β production, and inflammation. NLRP3 activation requires two signals. The first ...

Pannexin-1 promotes NLRP3 activation during apoptosis but is dispensable for canonical or Non-canonical inflammasome activation.

Inflammasomes are multimeric protein complex that assemble in the cytosol upon microbial infection or cellular stress. Upon activation, inflammasomes drive the maturation of proinflammatory cytokines ...

Modulation of calcium signaling pathway by hepatitis C virus core protein stimulates NLRP3 inflammasome activation.

Hepatitis C virus (HCV) infection remains a major cause of hepatic inflammation and liver disease. HCV triggers NLRP3 inflammasome activation and interleukin-1β (IL-1β) production from hepatic macro...

UFL1 modulates NLRP3 inflammasome activation and protects against pyroptosis in LPS-stimulated bovine mammary epithelial cells.

UFL1 was identified as a key regulator of cellular stress, which was found to possess anti-inflammatory and cytoprotection effect in LPS-stimulated bovine mammary epithelial cells in our previous stud...

NLRP3 inflammasome as a treatment target in atherosclerosis: A focus on statin therapy.

Activation of NOD-like receptor (NLR) family and pyrin domain containing 3 (NLRP3) inflammasome contributes to inflammation and may lead to atherosclerosis. The NLRP3 inflammasome as a molecular platf...

Clinical Trials [4051 Associated Clinical Trials listed on BioPortfolio]

A Role for RAGE/TXNIP/Inflammasome Axis in Alveolar Macrophage Activation During ARDS (RIAMA): a Proof-of-concept Clinical Study

RAGE (the receptor for advanced glycation end-products) is a marker of alveolar type I cell injury and a pivotal mediator of acute inflammation and innate immunity. RAGE pathway is highly ...

Characterization of Non-canonical Way in Inflammasome Monocytes of Patients With Severe Sepsis

Activation of caspase-4 and human caspase-5 (orthologs of caspase-11 in mice) in innate immune cells.

House Dust Mite Induced Inflammasome Activation on Corticosteroid Resistance

In this project, PBMCs will be isolated from HDM allergic and non allergic patient and then stimulated with HDM crude extract. The expression of inflammasome and the correlation of inflamm...

P2X7 Receptor, Inflammation and Neurodegenerative Diseases

Parkinson disease (PD) is a chronic degenerative disease characterized by a progressive loss of dopaminergic neurons in the substantia nigra. Its pathophysiological mechanisms are still pa...

Inflammasome Activation Via Circulating Metabolites

The clinical challenges confronting patients with HIV has shifted over the past 10 years from acquired immunodeficiency syndrome to chronic diseases including atherosclerosis, neurocogniti...

Medical and Biotech [MESH] Definitions

An NLR protein that contains an N-terminal PYRIN DOMAIN and ATP-binding site and 9 C-terminal LEUCINE-rich repeats; it is expressed primarily by MACROPHAGES. It is a core component of the INFLAMMASOME and directs its assembly in response to pathogen infection and damage-associated stimuli. Mutations in the NLRP3 gene are associated with FAMILIAL COLD AUTOINFLAMMATORY SYNDROME.

Type of programmed cell death associated with infection by intracellular pathogens. It is characterized by INFLAMMASOME formation; activation of CASPASE 1; and CYTOKINES mediated inflammation.

A NOD-signaling adaptor protein that contains a C-terminal leucine-rich domain which recognizes bacterial PEPTIDOGLYCAN. It signals via an N-terminal caspase recruitment domain that interacts with other CARD SIGNALING ADAPTOR PROTEINS such as RIP SERINE-THEONINE KINASES. It plays a role in the host defense response by signaling the activation of CASPASES and the MAP KINASE SIGNALING SYSTEM.

Wnt proteins are a large family of secreted glycoproteins that play essential roles in EMBRYONIC AND FETAL DEVELOPMENT, and tissue maintenance. They bind to FRIZZLED RECEPTORS and act as PARACRINE PROTEIN FACTORS to initiate a variety of SIGNAL TRANSDUCTION PATHWAYS. The canonical Wnt signaling pathway stabilizes the transcriptional coactivator BETA CATENIN.

A NOD signaling adaptor protein that contains two C-terminal leucine-rich domains which recognize bacterial PEPTIDOGLYCAN. It signals via an N-terminal capase recruitment domain that interacts with other CARD SIGNALING ADAPTOR PROTEINS such as RIP SERINE-THEONINE KINASES. The protein plays a role in the host defense response by signaling the activation of CASPASES and the MAP KINASE SIGNALING SYSTEM. Mutations of the gene encoding the nucleotide oligomerization domain 2 protein have been associated with increased susceptibility to CROHN DISEASE.

Quick Search

DeepDyve research library

Relevant Topics

Tropical Medicine
Tropical Medicine is the study of diseases more commonly found in tropical regions than elsewhere. Examples of these diseases are malaria, yellow fever, Chagas disease, Dengue, Helminths, African trypanosomiasis, Leishmaniasis, Leprosy, Lymphatic filaria...

Biological Therapy
Biological therapy involves the use of living organisms, substances derived from living organisms, or laboratory-produced versions of such substances to treat disease. Some biological therapies for cancer use vaccines or bacteria to stimulate the body&rs...

Searches Linking to this Article