Shivangi Rastogi won 2nd place at the UMD Postdoctoral Research Symposium for her poster titled “The serine/threonine protein kinase PknF of Mycobacterium tuberculosis represses bacterial virulence in mice.” Shivangi is an Assistant Research Scientist in the Briken Lab.
Poster blurb- Mycobacterium tuberculosis (Mtb) has evolved strategies to evade host innate immunity and persist inside host cells. We have previously demonstrated that Mtb inhibits NLRP3 inflammasome activation and subsequent IL-1β production via serine/threonine kinase PknF, as the pknF deletion mutant (Mtb∆PknF) induces higher IL-1β production and enhanced pyroptosis in macrophages and dendritic cells compared to Mtb-infected cells. However, the role of PknF during in vivo infection has not yet been established. Here, we examine how pknF deletion affects the pathogenicity of Mtb in wild-type (WT) and nlpr3-/- C57BL/6 mice. We show that in WT and nlpr3-/- mice, the infection with Mtb∆PknF results in higher bacterial loads in the lungs, bronchoalveolar lavage fluid, and spleens on days 28 and 120 post-infection compared to Mtb-infected mice. Histopathological analysis of mouse lungs on days 28 and 120 post-infection shows an increased infiltration of immune cells in Mtb∆PknF-infected mice compared to Mtb-infected mice. Mice infected with Mtb∆PknF exhibit an increased accumulation of foamy macrophages in the lungs, which correlates with increased cell death. Finally, we investigated the virulence of Mtb compared to Mtb∆PknF in a susceptible mouse model using sst1-/- mice. Survival studies revealed that the Mtb∆PknF strain killed the mice more rapidly than the Mtb strain at both low-dose and high-dose infections. In conclusion, our results using two different mouse models show that PknF limits the virulence of Mtb during in vivo infection and is essential for suppressing the NLRP3 inflammasome activation.