Differential cytokine gene expression according to outcome in a hamster model of leptospirosis.
BACKGROUND: Parameters predicting the evolution of leptospirosis would be useful for clinicians, as well as to better understand severe leptospirosis, but are scarce and rarely validated. Because severe leptospirosis includes septic shock, similarities with predictors evidenced for sepsis and septic...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-01-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | http://europepmc.org/articles/PMC2797601?pdf=render |
| _version_ | 1828750347924930560 |
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| author | Frédérique Vernel-Pauillac Cyrille Goarant |
| author_facet | Frédérique Vernel-Pauillac Cyrille Goarant |
| author_sort | Frédérique Vernel-Pauillac |
| collection | DOAJ |
| description | BACKGROUND: Parameters predicting the evolution of leptospirosis would be useful for clinicians, as well as to better understand severe leptospirosis, but are scarce and rarely validated. Because severe leptospirosis includes septic shock, similarities with predictors evidenced for sepsis and septic shock were studied in a hamster model. METHODOLOGY/PRINCIPAL FINDINGS: Using an LD50 model of leptospirosis in hamsters, we first determined that 3 days post-infection was a time-point that allowed studying the regulation of immune gene expression and represented the onset of the clinical signs of the disease. In the absence of tools to assess serum concentrations of immune effectors in hamsters, we determined mRNA levels of various immune genes, especially cytokines, together with leptospiraemia at this particular time-point. We found differential expression of both pro- and anti-inflammatory mediators, with significantly higher expression levels of tumor necrosis factor alpha, interleukin 1alpha, cyclo-oxygenase 2 and interleukin 10 genes in nonsurvivors compared to survivors. Higher leptospiraemia was also observed in nonsurvivors. Lastly, we demonstrated the relevance of these results by comparing their respective expression levels using a LD100 model or an isogenic high-passage nonvirulent variant. CONCLUSIONS/SIGNIFICANCE: Up-regulated gene expression of both pro- and anti-inflammatory immune effectors in hamsters with fatal outcome in an LD50 model of leptospirosis, together with a higher Leptospira burden, suggest that these gene expression levels could be predictors of adverse outcome in leptospirosis. |
| first_indexed | 2024-12-10T20:36:51Z |
| format | Article |
| id | doaj.art-0303c4a4b2ac43c583ffd0af24955a7d |
| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-12-10T20:36:51Z |
| publishDate | 2010-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-0303c4a4b2ac43c583ffd0af24955a7d2022-12-22T01:34:30ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352010-01-0141e58210.1371/journal.pntd.0000582Differential cytokine gene expression according to outcome in a hamster model of leptospirosis.Frédérique Vernel-PauillacCyrille GoarantBACKGROUND: Parameters predicting the evolution of leptospirosis would be useful for clinicians, as well as to better understand severe leptospirosis, but are scarce and rarely validated. Because severe leptospirosis includes septic shock, similarities with predictors evidenced for sepsis and septic shock were studied in a hamster model. METHODOLOGY/PRINCIPAL FINDINGS: Using an LD50 model of leptospirosis in hamsters, we first determined that 3 days post-infection was a time-point that allowed studying the regulation of immune gene expression and represented the onset of the clinical signs of the disease. In the absence of tools to assess serum concentrations of immune effectors in hamsters, we determined mRNA levels of various immune genes, especially cytokines, together with leptospiraemia at this particular time-point. We found differential expression of both pro- and anti-inflammatory mediators, with significantly higher expression levels of tumor necrosis factor alpha, interleukin 1alpha, cyclo-oxygenase 2 and interleukin 10 genes in nonsurvivors compared to survivors. Higher leptospiraemia was also observed in nonsurvivors. Lastly, we demonstrated the relevance of these results by comparing their respective expression levels using a LD100 model or an isogenic high-passage nonvirulent variant. CONCLUSIONS/SIGNIFICANCE: Up-regulated gene expression of both pro- and anti-inflammatory immune effectors in hamsters with fatal outcome in an LD50 model of leptospirosis, together with a higher Leptospira burden, suggest that these gene expression levels could be predictors of adverse outcome in leptospirosis.http://europepmc.org/articles/PMC2797601?pdf=render |
| spellingShingle | Frédérique Vernel-Pauillac Cyrille Goarant Differential cytokine gene expression according to outcome in a hamster model of leptospirosis. PLoS Neglected Tropical Diseases |
| title | Differential cytokine gene expression according to outcome in a hamster model of leptospirosis. |
| title_full | Differential cytokine gene expression according to outcome in a hamster model of leptospirosis. |
| title_fullStr | Differential cytokine gene expression according to outcome in a hamster model of leptospirosis. |
| title_full_unstemmed | Differential cytokine gene expression according to outcome in a hamster model of leptospirosis. |
| title_short | Differential cytokine gene expression according to outcome in a hamster model of leptospirosis. |
| title_sort | differential cytokine gene expression according to outcome in a hamster model of leptospirosis |
| url | http://europepmc.org/articles/PMC2797601?pdf=render |
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