Innate immune responses to gut microbiota differ between oceanic and freshwater threespine stickleback populations
Animal hosts must co-exist with beneficial microbes while simultaneously being able to mount rapid, non-specific, innate immune responses to pathogenic microbes. How this balance is achieved is not fully understood, and disruption of this relationship can lead to disease. Excessive inflammatory resp...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2016-02-01
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| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/9/2/187 |
| _version_ | 1819237251623682048 |
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| author | Kathryn Milligan-Myhre Clayton M. Small Erika K. Mittge Meghna Agarwal Mark Currey William A. Cresko Karen Guillemin |
| author_facet | Kathryn Milligan-Myhre Clayton M. Small Erika K. Mittge Meghna Agarwal Mark Currey William A. Cresko Karen Guillemin |
| author_sort | Kathryn Milligan-Myhre |
| collection | DOAJ |
| description | Animal hosts must co-exist with beneficial microbes while simultaneously being able to mount rapid, non-specific, innate immune responses to pathogenic microbes. How this balance is achieved is not fully understood, and disruption of this relationship can lead to disease. Excessive inflammatory responses to resident microbes are characteristic of certain gastrointestinal pathologies such as inflammatory bowel disease (IBD). The immune dysregulation of IBD has complex genetic underpinnings that cannot be fully recapitulated with single-gene-knockout models. A deeper understanding of the genetic regulation of innate immune responses to resident microbes requires the ability to measure immune responses in the presence and absence of the microbiota using vertebrate models with complex genetic variation. Here, we describe a new gnotobiotic vertebrate model to explore the natural genetic variation that contributes to differences in innate immune responses to microbiota. Threespine stickleback, Gasterosteus aculeatus, has been used to study the developmental genetics of complex traits during the repeated evolution from ancestral oceanic to derived freshwater forms. We established methods to rear germ-free stickleback larvae and gnotobiotic animals monoassociated with single bacterial isolates. We characterized the innate immune response of these fish to resident gut microbes by quantifying the neutrophil cells in conventionally reared monoassociated or germ-free stickleback from both oceanic and freshwater populations grown in a common intermediate salinity environment. We found that oceanic and freshwater fish in the wild and in the laboratory share many intestinal microbial community members. However, oceanic fish mount a strong immune response to residential microbiota, whereas freshwater fish frequently do not. A strong innate immune response was uniformly observed across oceanic families, but this response varied among families of freshwater fish. The gnotobiotic stickleback model that we have developed therefore provides a platform for future studies mapping the natural genetic basis of the variation in immune response to microbes. |
| first_indexed | 2024-12-23T13:17:22Z |
| format | Article |
| id | doaj.art-f43200b055044aec9dd7ff9adab2e6be |
| institution | Directory Open Access Journal |
| issn | 1754-8411 1754-8403 |
| language | English |
| last_indexed | 2024-12-23T13:17:22Z |
| publishDate | 2016-02-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-f43200b055044aec9dd7ff9adab2e6be2022-12-21T17:45:33ZengThe Company of BiologistsDisease Models & Mechanisms1754-84111754-84032016-02-019218719810.1242/dmm.021881021881Innate immune responses to gut microbiota differ between oceanic and freshwater threespine stickleback populationsKathryn Milligan-Myhre0Clayton M. Small1Erika K. Mittge2Meghna Agarwal3Mark Currey4William A. Cresko5Karen Guillemin6 Biology Department, Institute of Ecology and Evolution, University of Oregon, Eugene, OR 97403, USA Biology Department, Institute of Ecology and Evolution, University of Oregon, Eugene, OR 97403, USA Biology Department, Institute of Molecular Biology, University of Oregon, Eugene, OR 97403, USA Biology Department, Institute of Molecular Biology, University of Oregon, Eugene, OR 97403, USA Biology Department, Institute of Ecology and Evolution, University of Oregon, Eugene, OR 97403, USA Biology Department, Institute of Ecology and Evolution, University of Oregon, Eugene, OR 97403, USA Biology Department, Institute of Molecular Biology, University of Oregon, Eugene, OR 97403, USA Animal hosts must co-exist with beneficial microbes while simultaneously being able to mount rapid, non-specific, innate immune responses to pathogenic microbes. How this balance is achieved is not fully understood, and disruption of this relationship can lead to disease. Excessive inflammatory responses to resident microbes are characteristic of certain gastrointestinal pathologies such as inflammatory bowel disease (IBD). The immune dysregulation of IBD has complex genetic underpinnings that cannot be fully recapitulated with single-gene-knockout models. A deeper understanding of the genetic regulation of innate immune responses to resident microbes requires the ability to measure immune responses in the presence and absence of the microbiota using vertebrate models with complex genetic variation. Here, we describe a new gnotobiotic vertebrate model to explore the natural genetic variation that contributes to differences in innate immune responses to microbiota. Threespine stickleback, Gasterosteus aculeatus, has been used to study the developmental genetics of complex traits during the repeated evolution from ancestral oceanic to derived freshwater forms. We established methods to rear germ-free stickleback larvae and gnotobiotic animals monoassociated with single bacterial isolates. We characterized the innate immune response of these fish to resident gut microbes by quantifying the neutrophil cells in conventionally reared monoassociated or germ-free stickleback from both oceanic and freshwater populations grown in a common intermediate salinity environment. We found that oceanic and freshwater fish in the wild and in the laboratory share many intestinal microbial community members. However, oceanic fish mount a strong immune response to residential microbiota, whereas freshwater fish frequently do not. A strong innate immune response was uniformly observed across oceanic families, but this response varied among families of freshwater fish. The gnotobiotic stickleback model that we have developed therefore provides a platform for future studies mapping the natural genetic basis of the variation in immune response to microbes.http://dmm.biologists.org/content/9/2/187NeutrophilsGnotobioticSticklebackAnimal modelGerm-freeFish |
| spellingShingle | Kathryn Milligan-Myhre Clayton M. Small Erika K. Mittge Meghna Agarwal Mark Currey William A. Cresko Karen Guillemin Innate immune responses to gut microbiota differ between oceanic and freshwater threespine stickleback populations Disease Models & Mechanisms Neutrophils Gnotobiotic Stickleback Animal model Germ-free Fish |
| title | Innate immune responses to gut microbiota differ between oceanic and freshwater threespine stickleback populations |
| title_full | Innate immune responses to gut microbiota differ between oceanic and freshwater threespine stickleback populations |
| title_fullStr | Innate immune responses to gut microbiota differ between oceanic and freshwater threespine stickleback populations |
| title_full_unstemmed | Innate immune responses to gut microbiota differ between oceanic and freshwater threespine stickleback populations |
| title_short | Innate immune responses to gut microbiota differ between oceanic and freshwater threespine stickleback populations |
| title_sort | innate immune responses to gut microbiota differ between oceanic and freshwater threespine stickleback populations |
| topic | Neutrophils Gnotobiotic Stickleback Animal model Germ-free Fish |
| url | http://dmm.biologists.org/content/9/2/187 |
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