Work

Macro meets T: Signaling Lymphocyte Activation Molecule Family Member 1 (SLAMF1) promotes protective immunity against Mtb through Macrophage-T cell interaction 2327

Year: 2025

Type: article

Abstract: Description Effective control of Mycobacterium tuberculosis (Mtb) by the host necessitates efficient T-cells and macrophages (MΦ) interaction. In an RNA-seq screen, we found that SLAMF1 was highly induced in infected murine bone marrow-derived MΦs (BMDM), when co-cultured with CD4 T cells. SLAMF1 functions as a homophilic receptor. We hypothesized that SLAMF1 is vital for mediating MΦ-T cell interaction & Mtb control. We found that antigen-specific CD4 T cells promoted SLAMF1 surface expression in the infected MΦs, which depends on direct contact with T-cells. In vivo, SLAMF1 expression was abrogated in Mtb-infected monocytes and monocyte-derived cells (MDCs) of Tcra-/- and Rag-/- mice but was restored by the adoptive transfer of naïve CD4 T cells into Mtb-infected Tcra-/- mice. Lung cell immunophenotyping showed elevated SLAMF1 expression in both CD4 and CD8 T cells and infected myeloid cells of WT mice. Analysis of bacterial burden in the lungs of WT and Slamf1-/- KO (SKO) mice showed a higher bacterial load in SKO. Moreover, infected SKO mice exhibited elevated T cells and myeloid cell numbers, dysregulated inflammatory cytokine production & higher mortality rates upon Mtb infection than the WT mice. Finally, using the redox-sensitive reporter Mtb strain, we discovered that Mtb experiences lesser oxidative stress in SKO MΦ, demonstrating ROS production defect in the absence of SLAMF1. Thus, SLAMF1 engagement on MΦs and T-cells mediates protective immunity against Mtb infection. Funding Sources NIH R21 AI155380, ROI GR0035225 Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.254