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Pertussis, caused by Bordetella pertussis, is a reemerging disease that can produce severe disease manifestations in infants, including pulmonary hypertension (PH). B. pertussis-induced PH is a major risk factor for infection-induced death, but the molecular mechanisms promoting PH are unknown and there is no effective treatment. We examined B. pertussis-induced PH in infant and adult mouse models of pertussis by Fulton index, right heart catheterization, or Doppler echocardiogram. Our results demonstrate that B. pertussis-induced PH is age related and dependent on the expression of pertussis toxin by the bacterium. Hence, pertussis toxin-targeting treatments may ameliorate PH and fatal infant infection.
Karen M Scanlon; Ling Chen; Nicholas H Carbonetti. Pertussis Toxin Promotes Pulmonary Hypertension in an Infant Mouse Model of Bordetella pertussis Infection. The Journal of Infectious Diseases 2021, 1 .
AMA StyleKaren M Scanlon, Ling Chen, Nicholas H Carbonetti. Pertussis Toxin Promotes Pulmonary Hypertension in an Infant Mouse Model of Bordetella pertussis Infection. The Journal of Infectious Diseases. 2021; ():1.
Chicago/Turabian StyleKaren M Scanlon; Ling Chen; Nicholas H Carbonetti. 2021. "Pertussis Toxin Promotes Pulmonary Hypertension in an Infant Mouse Model of Bordetella pertussis Infection." The Journal of Infectious Diseases , no. : 1.
Type I and III IFNs play diverse roles in bacterial infections, being protective for some but deleterious for others. Using RNA-sequencing transcriptomics we investigated lung gene expression responses to Bordetella pertussis infection in adult mice, revealing that type I and III IFN pathways may play an important role in promoting inflammatory responses. In B. pertussis–infected mice, lung type I/III IFN responses correlated with increased proinflammatory cytokine expression and with lung inflammatory pathology. In mutant mice with increased type I IFN receptor (IFNAR) signaling, B. pertussis infection exacerbated lung inflammatory pathology, whereas knockout mice with defects in type I IFN signaling had lower levels of lung inflammation than wild-type mice. Curiously, B. pertussis–infected IFNAR1 knockout mice had wild-type levels of lung inflammatory pathology. However, in response to infection these mice had increased levels of type III IFN expression, neutralization of which reduced lung inflammation. In support of this finding, B. pertussis–infected mice with a knockout mutation in the type III IFN receptor (IFNLR1) and double IFNAR1/IFNLR1 knockout mutant mice had reduced lung inflammatory pathology compared with that in wild-type mice, indicating that type III IFN exacerbates lung inflammation. In marked contrast, infant mice did not upregulate type I or III IFNs in response to B. pertussis infection and were protected from lethal infection by increased type I IFN signaling. These results indicate age-dependent effects of type I/III IFN signaling during B. pertussis infection and suggest that these pathways represent targets for therapeutic intervention in pertussis.
Jeremy Ardanuy; Karen Scanlon; Ciaran Skerry; Serge Y. Fuchs; Nicholas H. Carbonetti. Age-Dependent Effects of Type I and Type III IFNs in the Pathogenesis of Bordetella pertussis Infection and Disease. The Journal of Immunology 2020, 204, 2192 -2202.
AMA StyleJeremy Ardanuy, Karen Scanlon, Ciaran Skerry, Serge Y. Fuchs, Nicholas H. Carbonetti. Age-Dependent Effects of Type I and Type III IFNs in the Pathogenesis of Bordetella pertussis Infection and Disease. The Journal of Immunology. 2020; 204 (8):2192-2202.
Chicago/Turabian StyleJeremy Ardanuy; Karen Scanlon; Ciaran Skerry; Serge Y. Fuchs; Nicholas H. Carbonetti. 2020. "Age-Dependent Effects of Type I and Type III IFNs in the Pathogenesis of Bordetella pertussis Infection and Disease." The Journal of Immunology 204, no. 8: 2192-2202.
Pertussis, caused by respiratory tract infection with the bacterial pathogen Bordetella pertussis, has long been considered to be a toxin-mediated disease. Bacteria adhere and multiply extracellularly in the airways and release several toxins, which have a variety of effects on the host, both local and systemic. Predominant among these toxins is pertussis toxin (PT), a multi-subunit protein toxin that inhibits signaling through a subset of G protein-coupled receptors in mammalian cells. PT activity has been linked with severe and lethal pertussis disease in young infants and a detoxified version of PT is a common component of all licensed acellular pertussis vaccines. The role of PT in typical pertussis disease in other individuals is less clear, but significant evidence supporting its contribution to pathogenesis has been accumulated from animal model studies. In this review we discuss the evidence indicating a role for PT in pertussis disease, focusing on its contribution to severe pertussis in infants, modulation of immune and inflammatory responses to infection, and the characteristic paroxysmal cough of pertussis.
Karen Scanlon; Ciaran Skerry; Nicholas Carbonetti. Association of Pertussis Toxin with Severe Pertussis Disease. Toxins 2019, 11, 373 .
AMA StyleKaren Scanlon, Ciaran Skerry, Nicholas Carbonetti. Association of Pertussis Toxin with Severe Pertussis Disease. Toxins. 2019; 11 (7):373.
Chicago/Turabian StyleKaren Scanlon; Ciaran Skerry; Nicholas Carbonetti. 2019. "Association of Pertussis Toxin with Severe Pertussis Disease." Toxins 11, no. 7: 373.