Christina L. Stallings

Washington University School of Medicine, St. Louis, MO

Mycobacterium tuberculosis is a leading cause of death due to infection globally. The alarming rise of drug-resistant tuberculosis (TB) cases has made it clear that we are not equipped to successfully battle the TB epidemic. In order to develop new therapies, a better understanding of M. tuberculosis pathogenesis is required. Both the disease outcome and the pathology of TB are driven by the immune response mounted in the host. Infection with M. tuberculosis elicits inflammatory host responses that are necessary to control infection but can also cause extensive tissue damage, and thus must be precisely balanced. Innate immune responses in particular play critical roles in coordinating inflammation, priming adaptive immune responses, and controlling bacterial replication during M. tuberculosis infection. This talk will highlight new discoveries of innate immune responses to M. tuberculosis that impact disease outcomes, how the pathogen responds to host inflammation to withstand stresses imposed by the immune system and tolerate exposure to antibiotics, and how these processes can be targeted in new treatment strategies for TB.

Selected references

• Zhu et al. CarD contributes to diverse gene expression outcomes throughout the genome of Mycobacterium tuberculosis. 2019 Proc Natl Acad Sci USA 116(27):13573-13581
• Flentie et al. Chemical disarming of isoniazid resistance in Mycobacterium tuberculosis. 2019 Proc Natl Acad Sci USA 116(21):10510-10517
• Huynh et al. Bhlhe40 is an essential repressor of IL-10 during Mycobacterium tuberculosis infection. 2018 J Exp Med 215(7):1823-1838
• Nair et al. Irg1 expression in myeloid cells prevents immunopathology during M. tuberculosis infection. 2018 J Exp Med 215(4):1035-1045
• Mann et al. Rv0004 is a new essential member of the mycobacterial DNA replication machinery. 2017 PLoS Genet 13(11):e1007115
• Kimmey et al. Unique role for ATG5 in neutrophil-mediated immunopathology during M. tuberculosis infection. 2015 Nature 528(7583):565-9