The interaction of macrophages and CD8 T cells in bronchoalveolar lavage fluid is associated with latent tuberculosis infection

Abstract

Mycobacterium tuberculosis (Mtb) infection, including active tuberculosis (TB) and latent Mtb infection (LTBI), leads to diverse outcomes owing to different host immune responses. However, the immune mechanisms that govern the progression from LTBI to TB remain poorly defined in humans. Here, we profiled the lung immune cell populations within the bronchoalveolar lavage fluid (BALF) from patients with LTBI or TB using single-cell RNA sequencing (scRNA-seq). We found that Mtb infection substantially changed the immune cell compartments in the BALF, especially for the three subsets of macrophages, monocyte macrophage (MM)-CCL23, MM-FCN1, and MM-SPP1, which were found to be associated with the disease status of TB infection. Notably, MM-CCL23 cells derived from monocytes after stimulation with Mtb were characterized by high levels of chemokine ( CCL23 and CXCL5 ) production and might serve as a marker for Mtb infection. The MM-CCL23 population mainly recruited CD8-CCR6 T cells through CCL20/CCR6, which was a prominent feature associated with protection immunity in LTBI. This study improves our understanding of the lung immune landscape during Mtb infection, which may inform future vaccine design for protective immunity.

Overexpression of LAG-3: a potential indicator of low immune function in tuberculosis

“…The single-cell clustering analysis conducted in non-human primate TB models revealed an elevated accumulation of LAG-3 on T cells and macrophages as TB infection and BCG injection duration extended, aligning with the outcomes from our subcomponent immune infiltration analysis ( Figures 3A-C , 5 , 6 ). A separate study indicated a relationship between the interaction of macrophages and CD8 T cells in bronchoalveolar lavage and latent TB infection ( Yang et al., 2023 ). The Monocyte macrophage (MM)-CCL23 pathway primarily attracted CD8-CCR6 T cells through the CCL20/CCR6 axis, a key feature associated with protective immunity in latent TB infection ( Yang et al., 2023 ).…”

Image_1.tif

“…A separate study indicated a relationship between the interaction of macrophages and CD8 T cells in bronchoalveolar lavage and latent TB infection (Yang et al, 2023). The Monocyte macrophage (MM)-CCL23 pathway primarily attracted CD8-CCR6 T cells through the CCL20/CCR6 axis, a key feature associated with protective immunity in latent TB infection (Yang et al, 2023). Boer MC et al observed that BCG vaccination induced KLRG1 expression on BCG-stimulated CD8+ T cells, leading to a significant reduction in proliferation (Boer et al, 2016).…”

“…The single-cell clustering analysis conducted in non-human primate TB models revealed an elevated accumulation of LAG-3 on T cells and macrophages as TB infection and BCG injection duration extended, aligning with the outcomes from our subcomponent immune infiltration analysis 5,6). A separate study indicated a relationship between the interaction of macrophages and CD8 T cells in bronchoalveolar lavage and latent TB infection (Yang et al, 2023). The Monocyte macrophage (MM)-CCL23 pathway primarily attracted CD8-CCR6 T cells through the CCL20/CCR6 axis, a key feature associated with protective immunity in latent TB infection (Yang et al, 2023).…”

Image_2.tif

“…A separate study indicated a relationship between the interaction of macrophages and CD8 T cells in bronchoalveolar lavage and latent TB infection (Yang et al, 2023). The Monocyte macrophage (MM)-CCL23 pathway primarily attracted CD8-CCR6 T cells through the CCL20/CCR6 axis, a key feature associated with protective immunity in latent TB infection (Yang et al, 2023). Boer MC et al observed that BCG vaccination induced KLRG1 expression on BCG-stimulated CD8+ T cells, leading to a significant reduction in proliferation (Boer et al, 2016).…”

“…The single-cell clustering analysis conducted in non-human primate TB models revealed an elevated accumulation of LAG-3 on T cells and macrophages as TB infection and BCG injection duration extended, aligning with the outcomes from our subcomponent immune infiltration analysis 5,6). A separate study indicated a relationship between the interaction of macrophages and CD8 T cells in bronchoalveolar lavage and latent TB infection (Yang et al, 2023). The Monocyte macrophage (MM)-CCL23 pathway primarily attracted CD8-CCR6 T cells through the CCL20/CCR6 axis, a key feature associated with protective immunity in latent TB infection (Yang et al, 2023).…”