Bacillus anthracis, the causative agent of anthrax, secretes lethal toxin that down-regulates immune functions. Translocation of B. anthracis across mucosal epithelia is key for its dissemination and pathogenesis. Group 3 innate lymphocytes (ILC3s) are important in mucosal barrier maintenance due to their expression of the cytokine IL-22, a critical regulator of tissue responses and repair during homeostasis and inflammation. We found that B. anthracis lethal toxin perturbed ILC3 function in vitro and in vivo, revealing an unknown IL-23-mediated MAPK signaling pathway. Lethal toxin had no effects on the canonical STAT3-mediated IL-23 signaling pathway. Rather lethal toxin triggered the loss of several MAP2K kinases, which correlated with reduced activation of downstream ERK1/2 and p38, respectively. Inhibition studies showed the importance of MAPK signaling in IL-23-mediated production of IL-22. Our finding that MAPK signaling is required for optimal IL-22 production in ILC3s may lead to new approaches for targeting IL-22 biology.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5695638 | PMC |
| http://dx.doi.org/10.1371/journal.ppat.1006690 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Development and Selection of Candidate Monoclonal Antibodies for the Detection of Clostridium botulinum Neurotoxin Serotype B Light Chain.
Protein Expr Purif
January 2025
Institute of Tropical Medicine, Joint Vietnam-Russia Tropical Science and Technology Research Center.
Botulinum neurotoxin, produced by the bacterium Clostridium botulinum, causes botulism, a severe, rapidly progressing, and potentially fatal condition. Swift detection of the toxin and timely administration of antitoxin antibodies are critical for effective treatment. The current standard for Botulinum toxin testing is the mouse lethality assay, but this method is time-consuming and requires live animals.
View Article and Find Full Text PDFMAP Kinase Signaling at the Crossroads of Inflammasome Activation.
Immunol Rev
January 2025
Department of Internal Medicine and Paediatrics, Ghent University, Ghent, Belgium.
Inflammasomes are crucial mediators of both antimicrobial host defense and inflammatory pathology, requiring stringent regulation at multiple levels. This review explores the pivotal role of mitogen-activated protein kinase (MAPK) signaling in modulating inflammasome activation through various regulatory mechanisms. We detail recent advances in understanding MAPK-mediated regulation of NLRP3 inflammasome priming, licensing and activation, with emphasis on MAPK-induced activator protein-1 (AP-1) signaling in NLRP3 priming, ERK1 and JNK in NLRP3 licensing, and TAK1 in connecting death receptor signaling to NLRP3 inflammasome activation.
View Article and Find Full Text PDFVenom composition, toxicity and cross-neutralization by PoliVal-ICP antivenom, of Mesoamerican jumping pitvipers genus Metlapilcoatlus (Viperidae: Crotalinae).
Trans R Soc Trop Med Hyg
January 2025
Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José 11501, Costa Rica.
Background: The genus Metlapilcoatlus was recently erected to include six species of stout venomous snakes, known as the jumping pitvipers, which inhabit mountainous areas of Mesoamerica. This group maintains affinity with Atropoides picadoi, another jumping pitviper with restricted distribution in Costa Rica and Panama. Although the venom of A.
View Article and Find Full Text PDFDeciphering pathogenicity and virulence of the first isolate from diabetic foot osteomyelitis.
Front Cell Infect Microbiol
January 2025
VBIC, INSERM U1047, University of Montpellier, Montpellier, France.
Introduction: This study identifies as a new coagulase-negative staphylococcal species isolated from diabetic foot osteomyelitis (DFOM) and provides an in-depth analysis of its pathogenic and virulence profile, as well as demonstrating its potential to cause infection.
Methods: The NSD001 strain was examined for its planktonic growth, biofilm production, and phagocytosis rates in murine macrophages compared to NSA739. Additionally, persistence and replication within human osteoblasts were investigated, while the zebrafish embryo model was employed to assess virulence.
Kupffer-Cell-Targeted Carboxylesterase 1f Knockdown Deteriorates Lipopolysaccharide/D-Galactosamine-Induced Acute Liver Failure Through Regulating Cellular Polarization in Mice.
Can J Gastroenterol Hepatol
December 2024
Department of Infectious Diseases, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Aims: Carboxylesterase (Ces)1f is implicated in protection against hepatic inflammation, but it is unclear whether the enzyme has an influence in polarization of Kupffer cells (KCs), the innate immune cells mediating hepatic inflammatory injury including acute liver failure (ALF). In the present study, we aim to explore KC polarization induced by Ces1f in mice with lipopolysaccharide/D-galactosamine (LPS/D-GalN)-induced ALF. We adopted a novel delivery system, β-1,3-D-glucan-encapsulated Endoporter-siRNA particles, to specifically target KC Ces1f knockdown via tail vein injection in mice.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!