A computational model tracks whole-lung Mycobacterium tuberculosis infection and predicts factors that inhibit dissemination
Fig 2
Process of Mtb infection and rules for granuloma dissemination and location within MultiGran.
A non-human primate is inoculated with Mtb, here tracked using different “barcodes” or IDs. These Mtb are taken up by resident macrophages, initiating an innate immune response. This response includes the secretion of various cytokines and chemokines that help prime and/or recruit other immune cells to the site of the infection, resulting in the formation of lung granulomas. The dynamics within each granuloma are governed by systems of ordinary differential equations. Occasionally, as a granuloma develops, it may disseminate—either locally or non-locally. In local dissemination, an Mtb-infected macrophage moves to another nearby location within the same lung lobe. In non-local dissemination, a free extracellular Mtb reaches the airways or is carried to a draining lymph node and then deposited at a site not necessarily near the original location; i.e., in a different lung lobe. The (x,y,z) positions of disseminated granulomas depend on the method of dissemination (i.e., local or nonlocal) and the position of the parent granuloma. Granuloma clusters can form when granulomas develop near each other and may grow into each other, or when one granuloma forms immediately adjacent to the original granuloma via local dissemination [3]. Granuloma clusters may contain more than one Mtb ID.