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Fatal Pertussis in the Neonatal Mouse Model Is Associated with Pertussis Toxin-Mediated Pathology beyond the Airways.
- Source :
-
Infection and immunity [Infect Immun] 2017 Oct 18; Vol. 85 (11). Date of Electronic Publication: 2017 Oct 18 (Print Publication: 2017). - Publication Year :
- 2017
-
Abstract
- In infants, Bordetella pertussis can cause severe disease, manifested as pronounced leukocytosis, pulmonary hypertension, and even death. The exact cause of death remains unknown, and no effective therapies for treating fulminant pertussis exist. In this study, a neonatal mouse model of critical pertussis is characterized, and a central role for pertussis toxin (PT) is described. PT promoted colonization, leukocytosis, T cell phenotypic changes, systemic pathology, and death in neonatal but not adult mice. Surprisingly, PT inhibited lung inflammatory pathology in neonates, a result which contrasts dramatically with observed PT-promoted pathology in adult mice. Infection with a PT-deficient strain induced severe pulmonary inflammation but not mortality in neonatal mice, suggesting that death in these mice was not associated with impaired lung function. Dissemination of infection beyond the lungs was also detected in neonatal mice, which may contribute to the observed systemic effects of PT. We propose that it is the systemic activity of pertussis toxin and not pulmonary pathology that promotes mortality in critical pertussis. In addition, we observed transmission of infection between neonatal mice, the first report of B. pertussis transmission in mice. This model will be a valuable tool to investigate causes of pertussis pathogenesis and identify potential therapies for critical pertussis.<br /> (Copyright © 2017 American Society for Microbiology.)
- Subjects :
- Age Factors
Animals
Animals, Newborn
Bordetella pertussis growth & development
Bordetella pertussis immunology
Disease Models, Animal
Humans
Infant
Leukocytosis immunology
Leukocytosis mortality
Leukocytosis pathology
Lung immunology
Lung pathology
Mice
Mice, Inbred BALB C
Neutrophils immunology
Neutrophils microbiology
Neutrophils pathology
Pertussis Toxin biosynthesis
Pertussis Toxin immunology
Survival Analysis
T-Lymphocytes immunology
T-Lymphocytes microbiology
T-Lymphocytes pathology
Whooping Cough immunology
Whooping Cough mortality
Whooping Cough pathology
Bordetella pertussis pathogenicity
Host-Pathogen Interactions
Leukocytosis microbiology
Lung microbiology
Pertussis Toxin toxicity
Whooping Cough microbiology
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5522
- Volume :
- 85
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Infection and immunity
- Publication Type :
- Academic Journal
- Accession number :
- 28784932
- Full Text :
- https://doi.org/10.1128/IAI.00355-17