Bacterial Strain–Dependent Dissociation of Cell Recruitment and Cell-to-Cell Spread in Early M. tuberculosis Infection
Beth Shoshana Zha, Ludovic Desvignes, Tawania Fergus, Amber Cornelius, Tan‐Yun Cheng, D. Branch Moody, J. Ernst
Abstract
Tuberculosis is a leading infectious disease killer worldwide and is caused by Mycobacterium tuberculosis. After exposure to M. tuberculosis, outcomes range from apparent elimination to active disease. Early innate immune responses may contribute to differences in outcomes, yet it is not known how bacterial strains alter the early dynamics of innate immune and T cell responses. We infected mice with distinct strains of M. tuberculosis and discovered striking differences in innate cellular recruitment, cell-to-cell spread of bacteria in the lungs, and kinetics of initiation of antigen-specific CD4 T cell responses. We also found that M. tuberculosis can spread beyond alveolar macrophages even before a large influx of inflammatory cells. These results provide evidence that distinct strains of M. tuberculosis can exhibit differential kinetics in cell-to-cell spread which is not directly linked to early recruitment of phagocytes but is subsequently linked to adaptive immune responses.