Differential resistance to nematode infection is associated with the genotype- and age-dependent pace of intestinal T cell homing
Abstract The resistance of inbred mice to nematode infections varies depending on the extent of protective Th2 responses. Here, we compared two mouse lines differing in resistance to infection with the enteric nematode Heligmosomoides polygyrus bakeri despite the similar instruction of GATA-3+ T eff...
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| Format: | Article |
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Nature Portfolio
2025-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-76204-4 |
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| author | Joshua Adjah Bhavya Kapse Hongwei Zhang Susanne Hartmann Sebastian Rausch |
| author_facet | Joshua Adjah Bhavya Kapse Hongwei Zhang Susanne Hartmann Sebastian Rausch |
| author_sort | Joshua Adjah |
| collection | DOAJ |
| description | Abstract The resistance of inbred mice to nematode infections varies depending on the extent of protective Th2 responses. Here, we compared two mouse lines differing in resistance to infection with the enteric nematode Heligmosomoides polygyrus bakeri despite the similar instruction of GATA-3+ T effector cells. Resistant BALB/c mice rapidly recruited high numbers of Th2 cells to the gut within the 1-week time frame required for larval development in the intestinal submucosa. C57BL/6 mice failed in the optimal control of early nematode fitness, with mucosal Th2 response peaking after 2 weeks when the larvae had left the tissue and relocated to the gut lumen as adult worms. The faster homing of Th2 cells to the gut of BALB/c mice is related to the extensive expression of the chemokine receptor CCR9 in GATA-3+ cells and higher frequencies of aldehyde dehydrogenase expressing dendritic cells present in mesenteric lymph nodes. Furthermore, nematode-infected older BALB/c mice displayed impaired resistance due to delayed mucosal homing of effector cells, which synergized with more numerous Th2/1 hybrid cells acting as IFN-γ-dependent confounders of type 2 responses. Hence, the distinct kinetics of effector cell recruitment to the infected gut and the quality of GATA-3+ T cell responses contribute to the genotype- and age-dependent resistance to intestinal nematode infections. |
| format | Article |
| id | doaj-art-d7d6510b17314c748bdf2282c2df1875 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-d7d6510b17314c748bdf2282c2df18752025-02-09T12:37:02ZengNature PortfolioScientific Reports2045-23222025-02-0115111310.1038/s41598-024-76204-4Differential resistance to nematode infection is associated with the genotype- and age-dependent pace of intestinal T cell homingJoshua Adjah0Bhavya Kapse1Hongwei Zhang2Susanne Hartmann3Sebastian Rausch4Department of Veterinary Medicine, Institute of Immunology, Freie Universität BerlinDepartment of Veterinary Medicine, Institute of Immunology, Freie Universität BerlinDepartment of Veterinary Medicine, Institute of Immunology, Freie Universität BerlinDepartment of Veterinary Medicine, Institute of Immunology, Freie Universität BerlinDepartment of Veterinary Medicine, Institute of Immunology, Freie Universität BerlinAbstract The resistance of inbred mice to nematode infections varies depending on the extent of protective Th2 responses. Here, we compared two mouse lines differing in resistance to infection with the enteric nematode Heligmosomoides polygyrus bakeri despite the similar instruction of GATA-3+ T effector cells. Resistant BALB/c mice rapidly recruited high numbers of Th2 cells to the gut within the 1-week time frame required for larval development in the intestinal submucosa. C57BL/6 mice failed in the optimal control of early nematode fitness, with mucosal Th2 response peaking after 2 weeks when the larvae had left the tissue and relocated to the gut lumen as adult worms. The faster homing of Th2 cells to the gut of BALB/c mice is related to the extensive expression of the chemokine receptor CCR9 in GATA-3+ cells and higher frequencies of aldehyde dehydrogenase expressing dendritic cells present in mesenteric lymph nodes. Furthermore, nematode-infected older BALB/c mice displayed impaired resistance due to delayed mucosal homing of effector cells, which synergized with more numerous Th2/1 hybrid cells acting as IFN-γ-dependent confounders of type 2 responses. Hence, the distinct kinetics of effector cell recruitment to the infected gut and the quality of GATA-3+ T cell responses contribute to the genotype- and age-dependent resistance to intestinal nematode infections.https://doi.org/10.1038/s41598-024-76204-4 |
| spellingShingle | Joshua Adjah Bhavya Kapse Hongwei Zhang Susanne Hartmann Sebastian Rausch Differential resistance to nematode infection is associated with the genotype- and age-dependent pace of intestinal T cell homing Scientific Reports |
| title | Differential resistance to nematode infection is associated with the genotype- and age-dependent pace of intestinal T cell homing |
| title_full | Differential resistance to nematode infection is associated with the genotype- and age-dependent pace of intestinal T cell homing |
| title_fullStr | Differential resistance to nematode infection is associated with the genotype- and age-dependent pace of intestinal T cell homing |
| title_full_unstemmed | Differential resistance to nematode infection is associated with the genotype- and age-dependent pace of intestinal T cell homing |
| title_short | Differential resistance to nematode infection is associated with the genotype- and age-dependent pace of intestinal T cell homing |
| title_sort | differential resistance to nematode infection is associated with the genotype and age dependent pace of intestinal t cell homing |
| url | https://doi.org/10.1038/s41598-024-76204-4 |
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