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The lung environment in pulmonary Mycobacterium tuberculosis infection influences local monocyte differentiation

ABSTRACT: Infection by Mycobacterium tuberculosis (Mtb) continues to cause significant mortality due to pathogen persistence in lung cells derived from blood monocytes. Since persistent blood monocytosis is a hallmark of tuberculosis and monocyte-derived lung subsets differ in their ability to restrict the growth of intracellular Mtb in mice, the ontogeny of these subsets could inform development of host-directed therapies. Recent literature suggests that circulating monocytes are heterogeneous and derive from mobilization of distinct bone marrow (BM) or spleen progenitors that direct local differentiation. However, the role of the inflamed lung environment on this process has not been addressed. We compared monopoiesis in the BM of Mtb-infected mice and uninfected controls and found that these monocyte pools had similar differentiation within the infected lung. While Mtb infection induced splenic monopoiesis, we found no impact on lung monocyte differentiation in splenectomized mice. However, when monocytes were transferred into Mtb-infected recipients with a distinct lung environment, we observed altered differentiation. We identified monocyte-derived lung subsets with unique gene expression, associated with specific spatial distributions and cell neighborhoods. These findings suggest that the local lung environment has a larger influence on the phenotypic diversity of monocyte-derived lung cells than does the peripheral environment.

ORGANISM(S): Mus musculus

PROVIDER: GSE336209 | GEO | 2026/06/26

REPOSITORIES: GEO

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