IL-17 can be protective or deleterious in murine pneumococcal pneumonia.
Streptococcus pneumoniae is the major bacterial cause of community-acquired pneumonia, and the leading agent of childhood pneumonia deaths worldwide. Nasal colonization is an essential step prior to infection. The cytokine IL-17 protects against such colonization and vaccines that enhance IL-17 resp...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-05-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1007099&type=printable |
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| author | Neil D Ritchie Ryan Ritchie Hannah K Bayes Tim J Mitchell Tom J Evans |
| author_facet | Neil D Ritchie Ryan Ritchie Hannah K Bayes Tim J Mitchell Tom J Evans |
| author_sort | Neil D Ritchie |
| collection | DOAJ |
| description | Streptococcus pneumoniae is the major bacterial cause of community-acquired pneumonia, and the leading agent of childhood pneumonia deaths worldwide. Nasal colonization is an essential step prior to infection. The cytokine IL-17 protects against such colonization and vaccines that enhance IL-17 responses to pneumococcal colonization are being developed. The role of IL-17 in host defence against pneumonia is not known. To address this issue, we have utilized a murine model of pneumococcal pneumonia in which the gene for the IL-17 cytokine family receptor, Il17ra, has been inactivated. Using this model, we show that IL-17 produced predominantly from γδ T cells protects mice against death from the invasive TIGR4 strain (serotype 4) which expresses a relatively thin capsule. However, in pneumonia produced by two heavily encapsulated strains with low invasive potential (serotypes 3 and 6B), IL-17 significantly enhanced mortality. Neutrophil uptake and killing of the serotype 3 strain was significantly impaired compared to the serotype 4 strain and depletion of neutrophils with antibody enhanced survival of mice infected with the highly encapsulated SRL1 strain. These data strongly suggest that IL-17 mediated neutrophil recruitment to the lungs clears infection from the invasive TIGR4 strain but that lung neutrophils exacerbate disease caused by the highly encapsulated pneumococcal strains. Thus, whilst augmenting IL-17 immune responses against pneumococci may decrease nasal colonization, this may worsen outcome during pneumonia caused by some strains. |
| format | Article |
| id | doaj-art-d887aee2d75345ebb00c2045e965f82e |
| institution | DOAJ |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2018-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-d887aee2d75345ebb00c2045e965f82e2025-08-20T02:45:28ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742018-05-01145e100709910.1371/journal.ppat.1007099IL-17 can be protective or deleterious in murine pneumococcal pneumonia.Neil D RitchieRyan RitchieHannah K BayesTim J MitchellTom J EvansStreptococcus pneumoniae is the major bacterial cause of community-acquired pneumonia, and the leading agent of childhood pneumonia deaths worldwide. Nasal colonization is an essential step prior to infection. The cytokine IL-17 protects against such colonization and vaccines that enhance IL-17 responses to pneumococcal colonization are being developed. The role of IL-17 in host defence against pneumonia is not known. To address this issue, we have utilized a murine model of pneumococcal pneumonia in which the gene for the IL-17 cytokine family receptor, Il17ra, has been inactivated. Using this model, we show that IL-17 produced predominantly from γδ T cells protects mice against death from the invasive TIGR4 strain (serotype 4) which expresses a relatively thin capsule. However, in pneumonia produced by two heavily encapsulated strains with low invasive potential (serotypes 3 and 6B), IL-17 significantly enhanced mortality. Neutrophil uptake and killing of the serotype 3 strain was significantly impaired compared to the serotype 4 strain and depletion of neutrophils with antibody enhanced survival of mice infected with the highly encapsulated SRL1 strain. These data strongly suggest that IL-17 mediated neutrophil recruitment to the lungs clears infection from the invasive TIGR4 strain but that lung neutrophils exacerbate disease caused by the highly encapsulated pneumococcal strains. Thus, whilst augmenting IL-17 immune responses against pneumococci may decrease nasal colonization, this may worsen outcome during pneumonia caused by some strains.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1007099&type=printable |
| spellingShingle | Neil D Ritchie Ryan Ritchie Hannah K Bayes Tim J Mitchell Tom J Evans IL-17 can be protective or deleterious in murine pneumococcal pneumonia. PLoS Pathogens |
| title | IL-17 can be protective or deleterious in murine pneumococcal pneumonia. |
| title_full | IL-17 can be protective or deleterious in murine pneumococcal pneumonia. |
| title_fullStr | IL-17 can be protective or deleterious in murine pneumococcal pneumonia. |
| title_full_unstemmed | IL-17 can be protective or deleterious in murine pneumococcal pneumonia. |
| title_short | IL-17 can be protective or deleterious in murine pneumococcal pneumonia. |
| title_sort | il 17 can be protective or deleterious in murine pneumococcal pneumonia |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1007099&type=printable |
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