THE ROLE OF T-BET IN LUNG INFECTION

Abstract

The T-box transcription factor, T-bet, regulates type 1 inflammatory responses against a range of infections. In this thesis, a previously unaddressed role of T-bet, to influenza virus and bacterial superinfection was demonstrated. T-bet deficiency did not adversely affect the efficacy of viral clearance or recovery compared to wild-type hosts. Instead, elevated IL-17 production by CD8+, CD4+ and γδ T cells, as well as increased infiltration of neutrophils in the lungs of influenza virus infected T-bet-/- mice contributed to survival advantage against secondary Streptococcus pneumoniae infection. During infection, inverse expression of T-bet and another homologous T-box factor, Eomesodermin (Eomes), in natural killer cells was observed. To further understand immunomodulatory mechanisms of T-bet, we further explored the regulatory effects of T-bet on Eomes. Together, our results provide the possibility of targeting T-bet activity for positive outcomes from lethal bacterial superinfection without affecting influenza viral clearance.