Toll-Like Receptor-4 Dependent Intestinal and Systemic Sequelae Following Peroral <i>Campylobacter coli</i> Infection of IL10 Deficient Mice Harboring a Human Gut Microbiota
Zoonotic <i>Campylobacter</i>, including <i>C. jejuni</i> and <i>C. coli</i>, are among the most prevalent agents of food-borne enteritis worldwide. The immunopathological sequelae of campylobacteriosis are caused by Toll-like Receptor-4 (TLR4)-dependent host immu...
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| Format: | Article |
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MDPI AG
2020-05-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/9/5/386 |
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| author | Sigri Kløve Claudia Genger Soraya Mousavi Dennis Weschka Stefan Bereswill Markus M. Heimesaat |
| author_facet | Sigri Kløve Claudia Genger Soraya Mousavi Dennis Weschka Stefan Bereswill Markus M. Heimesaat |
| author_sort | Sigri Kløve |
| collection | DOAJ |
| description | Zoonotic <i>Campylobacter</i>, including <i>C. jejuni</i> and <i>C. coli</i>, are among the most prevalent agents of food-borne enteritis worldwide. The immunopathological sequelae of campylobacteriosis are caused by Toll-like Receptor-4 (TLR4)-dependent host immune responses, induced by bacterial lipooligosaccharide (LOS). In order to investigate <i>C. coli</i>-host interactions, including the roles of the human gut microbiota and TLR4, upon infection, we applied a clinical acute campylobacteriosis model, and subjected secondary abiotic, TLR4-deficient IL10<sup>-/-</sup> mice and IL10<sup>-/-</sup> controls to fecal microbiota transplantation derived from human donors by gavage, before peroral <i>C. coli</i> challenge. Until day 21 post-infection, <i>C. coli</i> could stably colonize the gastrointestinal tract of human microbiota-associated (hma) mice of either genotype. TLR4-deficient IL10<sup>-/-</sup> mice, however, displayed less severe clinical signs of infection, that were accompanied by less distinct apoptotic epithelial cell and innate as well as adaptive immune cell responses in the colon, as compared to IL10<sup>-/-</sup> counterparts. Furthermore, <i>C. coli</i> infected IL10<sup>-/-</sup>, as opposed to TLR4-deficient IL10<sup>-/-</sup>, mice displayed increased pro-inflammatory cytokine concentrations in intestinal and, strikingly, systemic compartments. We conclude that pathogenic LOS might play an important role in inducing TLR4-dependent host immune responses upon <i>C. coli</i> infection, which needs to be further addressed in more detail. |
| first_indexed | 2024-03-10T19:45:47Z |
| format | Article |
| id | doaj.art-70568ab95f6440a8a16514473d44b6d1 |
| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-10T19:45:47Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathogens |
| spelling | doaj.art-70568ab95f6440a8a16514473d44b6d12023-11-20T00:52:04ZengMDPI AGPathogens2076-08172020-05-019538610.3390/pathogens9050386Toll-Like Receptor-4 Dependent Intestinal and Systemic Sequelae Following Peroral <i>Campylobacter coli</i> Infection of IL10 Deficient Mice Harboring a Human Gut MicrobiotaSigri Kløve0Claudia Genger1Soraya Mousavi2Dennis Weschka3Stefan Bereswill4Markus M. Heimesaat5Institute of Microbiology, Infectious Diseases and Immunology, Charité - University Medicine Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 12203 Berlin, GermanyInstitute of Microbiology, Infectious Diseases and Immunology, Charité - University Medicine Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 12203 Berlin, GermanyInstitute of Microbiology, Infectious Diseases and Immunology, Charité - University Medicine Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 12203 Berlin, GermanyInstitute of Microbiology, Infectious Diseases and Immunology, Charité - University Medicine Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 12203 Berlin, GermanyInstitute of Microbiology, Infectious Diseases and Immunology, Charité - University Medicine Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 12203 Berlin, GermanyInstitute of Microbiology, Infectious Diseases and Immunology, Charité - University Medicine Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 12203 Berlin, GermanyZoonotic <i>Campylobacter</i>, including <i>C. jejuni</i> and <i>C. coli</i>, are among the most prevalent agents of food-borne enteritis worldwide. The immunopathological sequelae of campylobacteriosis are caused by Toll-like Receptor-4 (TLR4)-dependent host immune responses, induced by bacterial lipooligosaccharide (LOS). In order to investigate <i>C. coli</i>-host interactions, including the roles of the human gut microbiota and TLR4, upon infection, we applied a clinical acute campylobacteriosis model, and subjected secondary abiotic, TLR4-deficient IL10<sup>-/-</sup> mice and IL10<sup>-/-</sup> controls to fecal microbiota transplantation derived from human donors by gavage, before peroral <i>C. coli</i> challenge. Until day 21 post-infection, <i>C. coli</i> could stably colonize the gastrointestinal tract of human microbiota-associated (hma) mice of either genotype. TLR4-deficient IL10<sup>-/-</sup> mice, however, displayed less severe clinical signs of infection, that were accompanied by less distinct apoptotic epithelial cell and innate as well as adaptive immune cell responses in the colon, as compared to IL10<sup>-/-</sup> counterparts. Furthermore, <i>C. coli</i> infected IL10<sup>-/-</sup>, as opposed to TLR4-deficient IL10<sup>-/-</sup>, mice displayed increased pro-inflammatory cytokine concentrations in intestinal and, strikingly, systemic compartments. We conclude that pathogenic LOS might play an important role in inducing TLR4-dependent host immune responses upon <i>C. coli</i> infection, which needs to be further addressed in more detail.https://www.mdpi.com/2076-0817/9/5/386Toll-like Receptor-4lipooligosaccharide<i>Campylobacter coli</i>campylobacteriosis modelhost–pathogen interactionhuman microbiota-associated IL-10<sup>-/-</sup> mice |
| spellingShingle | Sigri Kløve Claudia Genger Soraya Mousavi Dennis Weschka Stefan Bereswill Markus M. Heimesaat Toll-Like Receptor-4 Dependent Intestinal and Systemic Sequelae Following Peroral <i>Campylobacter coli</i> Infection of IL10 Deficient Mice Harboring a Human Gut Microbiota Pathogens Toll-like Receptor-4 lipooligosaccharide <i>Campylobacter coli</i> campylobacteriosis model host–pathogen interaction human microbiota-associated IL-10<sup>-/-</sup> mice |
| title | Toll-Like Receptor-4 Dependent Intestinal and Systemic Sequelae Following Peroral <i>Campylobacter coli</i> Infection of IL10 Deficient Mice Harboring a Human Gut Microbiota |
| title_full | Toll-Like Receptor-4 Dependent Intestinal and Systemic Sequelae Following Peroral <i>Campylobacter coli</i> Infection of IL10 Deficient Mice Harboring a Human Gut Microbiota |
| title_fullStr | Toll-Like Receptor-4 Dependent Intestinal and Systemic Sequelae Following Peroral <i>Campylobacter coli</i> Infection of IL10 Deficient Mice Harboring a Human Gut Microbiota |
| title_full_unstemmed | Toll-Like Receptor-4 Dependent Intestinal and Systemic Sequelae Following Peroral <i>Campylobacter coli</i> Infection of IL10 Deficient Mice Harboring a Human Gut Microbiota |
| title_short | Toll-Like Receptor-4 Dependent Intestinal and Systemic Sequelae Following Peroral <i>Campylobacter coli</i> Infection of IL10 Deficient Mice Harboring a Human Gut Microbiota |
| title_sort | toll like receptor 4 dependent intestinal and systemic sequelae following peroral i campylobacter coli i infection of il10 deficient mice harboring a human gut microbiota |
| topic | Toll-like Receptor-4 lipooligosaccharide <i>Campylobacter coli</i> campylobacteriosis model host–pathogen interaction human microbiota-associated IL-10<sup>-/-</sup> mice |
| url | https://www.mdpi.com/2076-0817/9/5/386 |
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