Pituitary Adenylate Cyclase-Activating Polypeptide Alleviates Intestinal, Extra-Intestinal and Systemic Inflammatory Responses during Acute <i>Campylobacter jejuni</i>-induced Enterocolitis in Mice
Human <i>Campylobacter jejuni</i> infections are emerging, and constitute a significant health burden worldwide. The ubiquitously expressed pituitary adenylate cyclase-activating polypeptide (PACAP) is well-known for its cell-protective and immunomodulatory effects. In our actual interve...
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MDPI AG
2020-09-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/9/10/805 |
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| author | Markus M. Heimesaat Soraya Mousavi Sigri Kløve Claudia Genger Dennis Weschka Andrea Tamas Dora Reglodi Stefan Bereswill |
| author_facet | Markus M. Heimesaat Soraya Mousavi Sigri Kløve Claudia Genger Dennis Weschka Andrea Tamas Dora Reglodi Stefan Bereswill |
| author_sort | Markus M. Heimesaat |
| collection | DOAJ |
| description | Human <i>Campylobacter jejuni</i> infections are emerging, and constitute a significant health burden worldwide. The ubiquitously expressed pituitary adenylate cyclase-activating polypeptide (PACAP) is well-known for its cell-protective and immunomodulatory effects. In our actual intervention study, we used an acute campylobacteriosis model and assessed the potential disease-alleviating effects of exogenous PACAP. Therefore, secondary abiotic IL-10<sup>−/−</sup> mice were perorally infected with <i>C. jejuni</i> and treated with synthetic PACAP38 intraperitoneally from day 2 until day 5 post-infection. Whereas PACAP did not interfere with the gastrointestinal colonization of the pathogen, mice from the PACAP group exhibited less severe clinical signs of <i>C. jejuni</i>-induced disease, as compared to mock controls, which were paralleled by alleviated apoptotic, but enhanced cell proliferative responses in colonic epithelia on day 6 post-infection. Furthermore, PACAP dampened the accumulation of macrophages and monocytes, but enhanced regulatory T cell responses in the colon, which were accompanied by less IFN-γ secretion in intestinal compartments in PACAP versus mock-treated mice. Remarkably, the inflammation-dampening properties of PACAP could also be observed in extra-intestinal organs, and strikingly, even the systemic circulation on day 6 post-infection. For the first time, we provide evidence that synthetic PACAP might be a promising candidate to combat acute campylobacteriosis and post-infectious sequelae. |
| first_indexed | 2024-03-10T15:57:20Z |
| format | Article |
| id | doaj.art-e87065736fb546e2915623d935305722 |
| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-10T15:57:20Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathogens |
| spelling | doaj.art-e87065736fb546e2915623d9353057222023-11-20T15:36:20ZengMDPI AGPathogens2076-08172020-09-0191080510.3390/pathogens9100805Pituitary Adenylate Cyclase-Activating Polypeptide Alleviates Intestinal, Extra-Intestinal and Systemic Inflammatory Responses during Acute <i>Campylobacter jejuni</i>-induced Enterocolitis in MiceMarkus M. Heimesaat0Soraya Mousavi1Sigri Kløve2Claudia Genger3Dennis Weschka4Andrea Tamas5Dora Reglodi6Stefan Bereswill7Institute 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, GermanyDepartment of Anatomy, MTA-PTE PACAP Research Team, Centre for Neuroscience, University of Pecs Medical School, 7691 Pecs, HungaryDepartment of Anatomy, MTA-PTE PACAP Research Team, Centre for Neuroscience, University of Pecs Medical School, 7691 Pecs, HungaryInstitute 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, GermanyHuman <i>Campylobacter jejuni</i> infections are emerging, and constitute a significant health burden worldwide. The ubiquitously expressed pituitary adenylate cyclase-activating polypeptide (PACAP) is well-known for its cell-protective and immunomodulatory effects. In our actual intervention study, we used an acute campylobacteriosis model and assessed the potential disease-alleviating effects of exogenous PACAP. Therefore, secondary abiotic IL-10<sup>−/−</sup> mice were perorally infected with <i>C. jejuni</i> and treated with synthetic PACAP38 intraperitoneally from day 2 until day 5 post-infection. Whereas PACAP did not interfere with the gastrointestinal colonization of the pathogen, mice from the PACAP group exhibited less severe clinical signs of <i>C. jejuni</i>-induced disease, as compared to mock controls, which were paralleled by alleviated apoptotic, but enhanced cell proliferative responses in colonic epithelia on day 6 post-infection. Furthermore, PACAP dampened the accumulation of macrophages and monocytes, but enhanced regulatory T cell responses in the colon, which were accompanied by less IFN-γ secretion in intestinal compartments in PACAP versus mock-treated mice. Remarkably, the inflammation-dampening properties of PACAP could also be observed in extra-intestinal organs, and strikingly, even the systemic circulation on day 6 post-infection. For the first time, we provide evidence that synthetic PACAP might be a promising candidate to combat acute campylobacteriosis and post-infectious sequelae.https://www.mdpi.com/2076-0817/9/10/805pituitary adenylate cyclase-activating polypeptide (PACAP)cellular protectionanti-apoptotic propertiesimmune modulationanti-inflammatory effectscell proliferation and regeneration |
| spellingShingle | Markus M. Heimesaat Soraya Mousavi Sigri Kløve Claudia Genger Dennis Weschka Andrea Tamas Dora Reglodi Stefan Bereswill Pituitary Adenylate Cyclase-Activating Polypeptide Alleviates Intestinal, Extra-Intestinal and Systemic Inflammatory Responses during Acute <i>Campylobacter jejuni</i>-induced Enterocolitis in Mice Pathogens pituitary adenylate cyclase-activating polypeptide (PACAP) cellular protection anti-apoptotic properties immune modulation anti-inflammatory effects cell proliferation and regeneration |
| title | Pituitary Adenylate Cyclase-Activating Polypeptide Alleviates Intestinal, Extra-Intestinal and Systemic Inflammatory Responses during Acute <i>Campylobacter jejuni</i>-induced Enterocolitis in Mice |
| title_full | Pituitary Adenylate Cyclase-Activating Polypeptide Alleviates Intestinal, Extra-Intestinal and Systemic Inflammatory Responses during Acute <i>Campylobacter jejuni</i>-induced Enterocolitis in Mice |
| title_fullStr | Pituitary Adenylate Cyclase-Activating Polypeptide Alleviates Intestinal, Extra-Intestinal and Systemic Inflammatory Responses during Acute <i>Campylobacter jejuni</i>-induced Enterocolitis in Mice |
| title_full_unstemmed | Pituitary Adenylate Cyclase-Activating Polypeptide Alleviates Intestinal, Extra-Intestinal and Systemic Inflammatory Responses during Acute <i>Campylobacter jejuni</i>-induced Enterocolitis in Mice |
| title_short | Pituitary Adenylate Cyclase-Activating Polypeptide Alleviates Intestinal, Extra-Intestinal and Systemic Inflammatory Responses during Acute <i>Campylobacter jejuni</i>-induced Enterocolitis in Mice |
| title_sort | pituitary adenylate cyclase activating polypeptide alleviates intestinal extra intestinal and systemic inflammatory responses during acute i campylobacter jejuni i induced enterocolitis in mice |
| topic | pituitary adenylate cyclase-activating polypeptide (PACAP) cellular protection anti-apoptotic properties immune modulation anti-inflammatory effects cell proliferation and regeneration |
| url | https://www.mdpi.com/2076-0817/9/10/805 |
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