Quantifying the Host-Pathogen Interface - A Multiscale Perspective on Infection, Immunomodulation, and Disease

Infection by intracellular pathogens such as Mycobacterium tuberculosis (Mtb), host immune response, and the occurrence of disease can be viewed as an emergent property resulting from the interaction of multiple molecular and cellular systems. While the tendency is to study microbial pathogens and their host targets individually or from a host or pathogen centric skew, the nature and dynamics of the interaction between the systems are key determinants in infection, immunity, and disease outcome. With the goal of integrating host and pathogen interactions, we develop multiscale experimental and theoretical models to explore pathogen adaptation to environmental stress, and chronic conditions plus comorbidities such as vitamin D deficiency or alcohol use that differentially modulate immune response to infection. Exploiting confocal imaging and 3D tissue culture models, our studies of infection are used to investigate both chemical and structural impacts of host-pathogen dynamics on the clearance of infection, disease onset and persistence. Results demonstrate the importance of host comorbidities, physiology, microenvironment, and biochemical dynamics in the modulation of infection outcome.

GRANT SUPPORT: Research supported in part by DTRA/HJF # FA8650-10-2-6062/subaward 2381, NIH/NHLBI award K25HL075105, and NSF MCB-1445470.