Modeling development of tertiary lymphoid structures in pulmonary tuberculosis by 3D profiling and trajectory analysis

They play important roles in infection control and cancer but the mechanisms controlling their formation and function remain only partly understood. Here, we combine high-plex imaging, serial-section 3D reconstruction, and optimal trajectory analysis modeling to reconstruct TLSs in human lung infected with Mycobacterium tuberculosis.

We find that TLSs are the extended and irregular , spatially heterogeneous structures shape of TLS whose state of maturation, as judged by germinal center (GC) organization, is poorly captured by 2D histopathology or spatial profilingprofiling, making assuagements of developmental stage (early, primary, or secondary) highly error prone. . Using 3D data, we show that TLSs having GCs are diverse in cellular composition, size, and morphology.