The lung tissue environment in Mycobacterium tuberculosis infection determines local monocyte differentiation
Year: 2026
Type: preprint
Abstract: Infection by Mycobacterium tuberculosis (Mtb) is characterized by pathogen persistence in lung cells derived from blood monocytes. Since monocyte-derived lung subsets differ in their ability to restrict the growth of intracellular Mtb in mice, understanding the ontogeny of these subsets can inform development of host-directed therapies. Circulating monocytes are proposed to be heterogeneous, arising from distinct bone marrow or spleen progenitors that direct local differentiation. However, the role of the Mtb-infected lung environment in this process has not been addressed. We found that infected and uninfected mice had similar bone marrow monopoiesis, resulting in equivalent monocyte differentiation within the infected lung. While pulmonary Mtb infection also induced splenic monopoiesis, we found no impact on lung monocyte differentiation in splenectomized mice. However, when wildtype monocytes were transferred into Mtb-infected Sp140 -/- recipients, in which excess Type I interferons and neutrophils alter the lung environment, we observed that donor-derived lung subsets resembled recipient-derived cells. In the lungs of Mtb-infected mice, 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.
Institution: University of California, San Francisco
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G4756830717, G5351157054, Cellular and Bacterial Dynamics in Tuberculosis, Impact of Mycobacterium tuberculosis on monocyte differentiation in vivo, Tuberculosis Research and Mentorship Program (TB RAMP II), Functional dynamics of TB granuloma architecture, Immunobiology of the normal and injured lung, UCSF-UCB Tuberculosis Research Advancement Center (TRAC), Multidisciplinary Training Program in Lung Disease
OpenAlex ID: W7166852050