Interleukin 10 controls the balance between tolerance, pathogen elimination and immunopathology in birds.
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| Publicado en: | bioRxiv (Jan 14, 2025) |
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| Autor principal: | |
| Otros Autores: | , , , , , , , , , , , , , , , , , , , |
| Publicado: |
Cold Spring Harbor Laboratory Press
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| Acceso en línea: | Citation/Abstract Full Text - PDF Full text outside of ProQuest |
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| 001 | 3155459028 | ||
| 003 | UK-CbPIL | ||
| 022 | |a 2692-8205 | ||
| 024 | 7 | |a 10.1101/2025.01.10.632125 |2 doi | |
| 035 | |a 3155459028 | ||
| 045 | 0 | |b d20250114 | |
| 100 | 1 | |a Meunier, Dominique | |
| 245 | 1 | |a Interleukin 10 controls the balance between tolerance, pathogen elimination and immunopathology in birds. | |
| 260 | |b Cold Spring Harbor Laboratory Press |c Jan 14, 2025 | ||
| 513 | |a Working Paper | ||
| 520 | 3 | |a Effective mucosal immunity in the intestine involves a fine balance between tolerance of the microbiome, recognition and elimination of pathogens, and inflammatory tissue injury. The anti-inflammatory cytokine IL10 regulates these processes in the intestines of mice and humans; the anti-inflammatory activity of IL10 is also conserved in birds. To determine the function of IL10 in avian mucosal immunity, we generated germ line modifications of the chicken IL10 locus to abolish or reduce IL10 expression. In vitro analysis of macrophage response to lipopolysaccharide confirmed the loss of IL10 protein expression, the lack of dosage compensation in heterozygotes, and prevention of autocrine inhibition of nitric oxide production in homozygous IL10 knockout macrophages. IL10-deficiency significantly altered the composition of the caecal microbiome, but unlike IL10-deficient mice and humans, IL10-deficient chickens did not exhibit spontaneous colitis. Following experimental challenge with Salmonella enterica serovar Typhimurium or Campylobacter jejuni in IL10-deficient chickens, enhanced clearance of the pathogens was associated with elevated transcription of pro-inflammatory genes and increased infiltration of inflammatory cells into gut mucosa. In IL10-deficient chickens challenged with the parasite Eimeria tenella, pathogen clearance was accelerated but caecal lesions were more severe and weight gain was compromised. Neither the heterozygous IL10 knockout nor a homozygous IL10 enhancer mutation had a major effect on pathogen clearance or inflammation in any of the challenge models. Our findings highlight the intrinsic compromise in mucosal immune response and have important implications for the development of strategies to combat avian and zoonotic pathogens in poultry.Competing Interest StatementMichael J McGrew is inventor on patent application WO 2020074915 for the iCaspase9 surrogate host chicken; the University of Edinburgh is the applicant. The other authors declare no competing interests. | |
| 653 | |a Dosage compensation | ||
| 653 | |a Pathogens | ||
| 653 | |a Immune clearance | ||
| 653 | |a Autocrine signalling | ||
| 653 | |a Patent applications | ||
| 653 | |a Anti-inflammatory agents | ||
| 653 | |a Mucosal immunity | ||
| 653 | |a Heterozygotes | ||
| 653 | |a Lipopolysaccharides | ||
| 653 | |a Immunological tolerance | ||
| 653 | |a Immune system | ||
| 653 | |a Macrophages | ||
| 653 | |a Interleukin 10 | ||
| 653 | |a Poultry | ||
| 653 | |a Colitis | ||
| 653 | |a Nitric oxide | ||
| 653 | |a Microbiomes | ||
| 653 | |a Immune response | ||
| 653 | |a Inflammation | ||
| 700 | 1 | |a Corona-Torres, Ricardo | |
| 700 | 1 | |a Boulton, Kay | |
| 700 | 1 | |a Wu, Zhiguang | |
| 700 | 1 | |a Ballantyne, Maeve | |
| 700 | 1 | |a Glendinning, Laura | |
| 700 | 1 | |a Anum Ali Ahmad | |
| 700 | 1 | |a Borowska, Dominika | |
| 700 | 1 | |a Taylor, Lorna | |
| 700 | 1 | |a Vervelde, Lonneke | |
| 700 | 1 | |a Jorge Del Pozo | |
| 700 | 1 | |a Vasilogianni, Marili | |
| 700 | 1 | |a Jaramillo-Ortiz, Jose | |
| 700 | 1 | |a Sanchez-Arsuaga, Gonzalo | |
| 700 | 1 | |a Psifidi, Androniki | |
| 700 | 1 | |a Tomley, Fiona | |
| 700 | 1 | |a Watson, Kellie A | |
| 700 | 1 | |a Mcgrew, Michael J | |
| 700 | 1 | |a Stevens, Mark P | |
| 700 | 1 | |a Blake, Damer P | |
| 700 | 1 | |a Hume, David A | |
| 773 | 0 | |t bioRxiv |g (Jan 14, 2025) | |
| 786 | 0 | |d ProQuest |t Biological Science Database | |
| 856 | 4 | 1 | |3 Citation/Abstract |u https://www.proquest.com/docview/3155459028/abstract/embedded/75I98GEZK8WCJMPQ?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text - PDF |u https://www.proquest.com/docview/3155459028/fulltextPDF/embedded/75I98GEZK8WCJMPQ?source=fedsrch |
| 856 | 4 | 0 | |3 Full text outside of ProQuest |u https://www.biorxiv.org/content/10.1101/2025.01.10.632125v1 |