As a specialized subset of intestinal epithelial cells (IECs), goblet cells (GCs) play an important role during the antibacterial response via mucin production. However, the regulatory mechanisms involved in GC differentiation and function during infection, particularly the role of immune cell-IEC cross-talk, remain largely unknown. In this study, using conditional knockout mice, we demonstrate that LTβR, expressed on IECs, is required for GC hyperplasia and mucin 2 (MUC2) expression during infection for host defense but not homeostatic maintenance in the naive state. Analysis of single gene-deficient mice revealed that the ligand lymphotoxin (LT), but not LIGHT, and type 3 innate lymphoid cells (ILC3s), but not conventional T cells, are required for MUC2-dependent control. Conditional deficiency of LT in ILC3s further confirmed the importance of LT signals derived from ILC3s. Lack of ILC3-derived LT or IEC-derived LTβR resulted in the defective expression of genes related to GC differentiation but was not correlated with IEC proliferation and cell death, which were found to be normal by Ki-67 and Annexin V staining. In addition, the alternative NF-κB signaling pathway (involving RelB) in IECs was found to be required for the expression of GC differentiation-related genes and and required for the anti- response. Therefore, our data together suggest a previously unrecognized ILC3-IEC interaction and LT-LTβR-RelB signaling axis governing GC differentiation and function during infection for host defense.
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http://dx.doi.org/10.4049/jimmunol.2000197 | DOI Listing |
Microbiol Spectr
January 2025
Department of Medicine, Diabetes Center of Excellence, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
Influenza A virus (IAV) is a respiratory pathogen with a segmented negative-sense RNA genome that can cause epidemics and pandemics. The host factors required for the complete IAV infectious cycle have not been fully identified. Here, we examined three host factors for their contributions to IAV infectivity.
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Department of Urology, The Fourth Affiliated Hospital of Soochow University, Suzhou Dushu Lake Hospital, Medical Center of Soochow University, Suzhou, 215000, China; Department of Urology, First Affiliated Hospital of Soochow University, Suzhou, 215006, China. Electronic address:
Activating the cGAS-STING pathway presents a promising strategy to enhance the innate immunity and combat the immunosuppressive tumor microenvironment. One key mechanism for triggering this pathway involves the release of damaged DNA fragments caused by nuclear DNA damage. However, conventional cGAS-STING agonists often suffer from limited nucleus-targeting efficiency and potential biotoxicity.
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February 2025
Department of Biological Sciences, College of Liberal Arts and Sciences, Wayne State University, Detroit, MI 48202.
The mammalian Hippo kinases, MST1 and MST2, regulate organ development and suppress tumor formation by balancing cell proliferation and death. In macrophages, inflammasomes detect molecular patterns from invading pathogens or damaged host cells and trigger programmed cell death. In addition to lytic pyroptosis, the signatures associated with apoptosis are induced by inflammasome activation, but how the inflammasomes coordinate different cell death processes remains unclear.
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January 2025
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Caspase family proteases and Toll/interleukin-1 receptor (TIR)-domain proteins have central roles in innate immunity and regulated cell death in humans. We describe a bacterial immune system comprising both a caspase-like protease and a TIR-domain protein. We found that the TIR protein, once it recognizes phage invasion, produces the previously unknown immune signaling molecule adenosine 5'-diphosphate-cyclo[N7:1'']-ribose (N7-cADPR).
View Article and Find Full Text PDFPLoS Pathog
January 2025
Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET). Córdoba, Argentina.
Tissue-repair regulatory T cells (trTregs) comprise a specialized cell subset essential for tissue homeostasis and repair. While well-studied in sterile injury models, their role in infection-induced tissue damage and antimicrobial immunity is less understood. We investigated trTreg dynamics during acute Trypanosoma cruzi infection, marked by extensive tissue damage and strong CD8+ immunity.
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