Role of Interferon-γ in promoting disease severity in neonatal Bordetella pertussis infection

• Published in: The Journal of immunology (1950) 2018-05, Vol.200 (1_Supplement), p.117-117.29
• Main Authors: Mitchell, Ashley E., Scanlon, Karen, Carbonetti, Nicholas
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.200.Supp.117.29

Pertussis is an infectious disease caused by the bacterial pathogen Bordetella pertussis. In recent years, there has been a re-emergence of pertussis disease. Pertussis morbidity is extensive and spans across all age groups, but a higher incidence of severe disease and mortality is exhibited in young infants. Mortality is associated with severe respiratory infection and other systemic secondary co-morbidities. The infant immune system has reduced capacity to generate proinflammatory/T-helper (Th) 1 cell polarizing responses. Secretion of Interferon gamma (IFN-γ), a Th1 polarizing cytokine, by immune cells plays a critical role in macrophage activation and microbicidal activity in the lung. Furthermore, B. pertussis respiratory challenge of adult IFN-γ receptor deficient mice results in systemic dissemination and lethality. We hypothesize that the dissemination and lethality observed in our neonatal mouse model is a result of inadequate IFN-γ signaling or production, which contribute to insufficient control of the infection. We found that B. pertussis infection results in a significantly lower level of transcription of IFN-γ in the lungs and increased bacterial dissemination in neonatal mice when compared to adult mice. Additionally, infected neonatal mice deficient in IL-10, a potent regulator of IFN-γ, showed reduced dissemination and significantly increased IFN-γ and other pro-inflammatory cytokines as compared to age-matched wild type mice. Future studies include characterization of IFN-γ secreting immune cells during infection. Results generated by this work will contribute to a better understanding of severe disease in infants, addressing the limitations of infant immunity and treatment options for pertussis.