Early alveolar macrophage response and IL-1R-dependent T cell priming determine transmissibility of Mycobacterium tuberculosis strains

Halting tuberculosis transmission is crucial to TB elimination. Here the authors implicate IL-1R dependent T cell priming as the underlying mechanism determining variability in transmission of Mycobacterium tuberculosis strains. Mechanisms underlying variability in transmission of Mycobacterium tuberculosis strains remain undefined. By characterizing high and low transmission strains of M.tuberculosis in mice, we show here that high transmission M.tuberculosis strain induce rapid IL-1R-dependent alveolar macrophage migration from the alveolar space into the interstitium and that this action is key to subsequent temporal events of early dissemination of bacteria to the lymph nodes, Th1 priming, granulomatous response and bacterial control. In contrast, IL-1R-dependent alveolar macrophage migration and early dissemination of bacteria to lymph nodes is significantly impeded in infection with low transmission M.tuberculosis strain; these events promote the development of Th17 immunity, fostering neutrophilic inflammation and increased bacterial replication. Our results suggest that by inducing granulomas with the potential to develop into cavitary lesions that aids bacterial escape into the airways, high transmission M.tuberculosis strain is poised for greater transmissibility. These findings implicate bacterial heterogeneity as an important modifier of TB disease manifestations and transmission.

Automated summary

In this study, the authors found that high transmission strains of Mycobacterium tuberculosis induce rapid migration of alveolar macrophages and early dissemination of bacteria to lymph nodes, resulting in greater transmissibility. In contrast, low transmission strains impede these processes and promote Th17 immunity, leading to neutrophilic inflammation and increased bacterial replication.