Macrophage-T cell interactions promote SLAMF1 expression for enhanced TB defense.

Publication date: Jul 23, 2025

CD4+ T cells are crucial for protective immunity to intracellular pathogens. In addition to secreting cytokines, CD4+ T cells promote control of Mycobacterium tuberculosis infection through cognate interactions with macrophages, but the mechanism has been unclear. Here, we show that SLAMF1/CD150 is highly and uniquely induced in macrophages by antigen-specific interactions with CD4+ T cells. In macrophages, SLAMF1 enhances the generation of reactive oxygen species and restricts Mtb replication. Mtb-infection of mice promotes SLAMF1 expression specifically on infected macrophages, not uninfected bystanders. SLAMF1 expression depends on adaptive immunity and also autophagy. Moreover, Slamf1 mice have higher Mtb burden and more rapid disease progression than wild type mice. Using Slamf1 conditional knock-out mice, we show that in vivo Slamf1 is specifically required in macrophages to restrict mycobacterial growth and limit IL-1β production. In macaques, macrophage SLAMFI expression also correlates with T cell responses and protection. Combined, these data demonstrate that SLAMF1 is a marker of macrophage-T cells interactions, and it promotes protection against Mtb.

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Concepts Keywords
Cytokines Adaptive Immunity
Higher Animals
Mice CD4-Positive T-Lymphocytes
Mycobacterial Cell Communication
Tuberculosis Female
Humans
Interleukin-1beta
Interleukin-1beta
Macrophages
Mice
Mice, Knockout
Mycobacterium tuberculosis
Slamf1 protein, mouse
Tuberculosis

Semantics

Type Source Name
disease IDO cell
disease MESH Mycobacterium tuberculosis infection
disease IDO replication
disease MESH infection
pathway REACTOME Autophagy
disease MESH disease progression
drug DRUGBANK Oxygen
disease IDO production
pathway KEGG Tuberculosis
disease MESH death
disease IDO host
disease MESH Infectious Diseases
disease MESH granulomas
disease MESH measles
pathway KEGG Measles
disease IDO bacteria
drug DRUGBANK Nitric Oxide

Original Article

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