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Ashley Mitchell

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Microbiology and Immunology

Area of Doctoral Study: Microbiology and Immunology

Undergraduate  Institute: Towson University

Graduate Institute: Towson University

Research Advisor: Marcela Pasetti, Ph.D.  and Nicholas Carbonetti, Ph.D.

Description of Research

Pertussis, or whooping cough, is an infectious disease caused by the bacterial pathogen Bordetella pertussis. Pertussis has re-emerged in recent years in part due to the failure of the acellular vaccine to provide lasting protective immunity. Although the morbidity associated with pertussis is extensive and spans across all age groups, a higher incidence of severe disease and mortality is exhibited in young infants. Mortality is associated with severe respiratory infection and secondary co-morbidities such as leukocytosis and pulmonary hypertension. The infant immune system has reduced capacity to generate proinflammatory/T helper (Th) 1 cell polarizing responses. The secretion of Interferon gamma (IFN-γ), a Th1 polarizing cytokine, by immune cells is known to play 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 IFN-γ protects against systemic dissemination observed during infection. Work performed in our lab demonstrates that B. pertussis infection results in markedly reduced transcription of IFN-γ in the lungs and increased bacterial dissemination in neonatal mice when compared to infected adult mice. Therefore, we hypothesize that the disease severity observed in infants is a result of defective IFN-γ signaling or production and is associated with a depressed Th1-inducing cytokine response. To address this hypothesis, we will compare IFN-γ expression levels in the local and systemic organs of both adult and neonatal mice infected with B. pertussis. Further studies will include characterizing IFN-γ signaling deficiencies in both the responder and producer cell populations in the lungs and systemic organs. 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 to pertussis.