A reaction-diffusion-drainage model to explore geometrical constraints during tuberculosis granulomas formation

Tuberculosis (TB) is one of the leading causes of death worldwide, with infection outcomes ranging from asymptomatic latent tuberculosis infection (LTBI) to severe active tuberculosis (ATB). Granuloma formation and its subsequent encapsulation inside pulmonary secondary lobules is a key mechanism that determines disease progression. In this work, we extend previous reaction-diffusion models of granuloma development by incorporating fibroblast drainage and collagen synthesis, two crucial mechanisms involved in the lesion encapsulation process. We explore the encapsulation dynamics using Finite Element Analysis simulations and introduce a geometrical hypothesis to explain the observed differences in TB lesion control between infants and adults. Our results suggest that infants, due to the smaller and more compact geometry of their secondary lobules, are more likely to rapidly isolate the infection, thus preventing lesion expansion and systemic dissemination. This work sets the stage for future whole-lung simulations aimed at linking microscopic encapsulation dynamics with macroscopic infection outcomes.