We defined the function of type I interferons (IFNs) in defense against reovirus strain type 1 Lang (T1L), which is a double-stranded RNA virus that infects Peyer's patches (PPs) after peroral inoculation of mice. T1L induced expression of mRNA for IFN-alpha, IFN-beta, and Mx-1 in PPs and caused localized intestinal infection that was cleared in 10 d. In contrast, T1L produced fatal systemic infection in IFNalphaR1 knockout (KO) mice with extensive cell loss in lymphoid tissues and necrosis of the intestinal mucosa. Studies of bone-marrow chimeric mice indicated an essential role for hematopoietic cells in IFN-dependent viral clearance. Dendritic cells (DCs), including conventional DCs (cDCs), were the major source of type I IFNs in PPs of reovirus-infected mice, whereas all cell types expressed the antiviral protein Mx-1. Neither NK cells nor signaling via Toll-like receptor 3 or MyD88 were essential for viral clearance. These data demonstrate a requirement for type I IFNs in the control of an intestinal viral infection and indicate that cDCs are a significant source of type I IFN production in vivo. Therefore, innate immunity in PPs is an essential component of host defense that limits systemic spread of pathogens that infect the intestinal mucosa.
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http://dx.doi.org/10.1084/jem.20061587 | DOI Listing |
J Exp Med
April 2025
Department of Immunology, Harvard Medical School, Boston, MA, USA.
Inflammatory cytokines are fundamental mediators of the organismal response to injury, infection, or other harmful stimuli. To elucidate the early and mostly direct transcriptional signatures of inflammatory cytokines, we profiled all immunologic cell types by RNAseq after systemic exposure to IL1β, IL6, and TNFα. Our results revealed a significant overlap in the responses, with broad divergence between myeloid and lymphoid cells, but with very few cell-type-specific responses.
View Article and Find Full Text PDFFront Cell Infect Microbiol
January 2025
Guangxi Key Laboratory for Polysaccharide Materials and Modifications, School of Marine Sciences and Biotechnology, Guangxi Minzu University, Nanning, Guangxi, China.
Interferon regulatory factor 7 (IRF7)-mediated type I interferon antiviral response is crucial for regulating the host following viral infection in chickens. Infectious bursal disease virus (IBDV) is a double-stranded RNA virus that induces immune suppression and high mortality rates in chickens aged 3-6 weeks. Previous studies have shown that IBDV infection antagonizes the type I interferon production to facilitate viral replication in the cell, and IRF7 signaling might play an important role.
View Article and Find Full Text PDFPediatr Rheumatol Online J
January 2025
Laboratory of Autoimmunity and Inflammation, Center for Clinical, Biomedical Research Foundation, Experimental Surgery and Translational Research, Academy of Athens, Athens, Greece.
Background: Type I interferonopathies including Aicardi-Goutiéres Syndrome (AGS) represent a heterogeneous group of clinical phenotypes. Herein, we present a Case with combined AGS and Cornelia de Lange Syndrome (CdLS)-a cohesinopathy-with comprehensive analysis of the immune and genomic abnormalities.
Case And Methods: A 20-year old man presented with chilblain lesions and resorption of distal phalanges of fingers and toes, somatic and psychomotor retardation, microcephaly, synophrys, hearing losing and other aberrancies consistent with the phenotype of CdLS.
Autoimmun Rev
January 2025
Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Electronic address:
Tuberculosis (TB), caused by Mycobacterium TB, is the most significant infectious cause of mortality across the globe. While TB disease can prey on immunocompetent individuals, it is more likely to occur in immunocompromised individuals. Immune-mediated inflammatory diseases (IMIDs) are a group of diseases (rheumatoid arthritis, inflammatory bowel disease, ankylosing spondylitis, psoriasis, hidradenitis suppurative, autoimmune blistering diseases, and others) where there may be a need for systemic immunosuppression to control the disease manifestations, treat symptoms and improve long term outcomes.
View Article and Find Full Text PDFJ Cell Mol Med
January 2025
Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China.
Accumulating research indicates that N6-methyladenosine (m6A) modification plays a pivotal role in colorectal cancer (CRC). Hence, investigating the m6A-related long noncoding RNAs (lncRNAs) significantly improves therapeutic strategies and prognostic assessments. This study aimed to develop and validate a prognostic model based on m6A-related lncRNAs to improve the prediction of clinical outcomes and identify potential immunological mechanisms in CRC.
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