Investigating the role of BHLHE40 in host responses to <i>Mycobacterium tuberculosis</i>infection and myeloid cell development.

Abstract We currently lack a complete understanding of the immune responses required to control Mycobacterium tuberculosis (Mtb) infection. Our lab has shown that transcription factor BHLHE40 is essential during Mtb Deletion Bhlhe40 in CD11c +lung macrophages and dendritic cells (DCs) sufficient increase mouse susceptibility infection, though role these infection unknown. Murine bone marrow cultured presence GM-CSF, an abundant cytokine lung, develop into populations +macrophages, DCs, granulocytes, all which express Bhlhe40. Using this system, we examined transcriptional before after exposure heat-killed understand how impacts cell development inflammatory responses. found WT mice, GM-CSF-cultured 9 distinct expression was for GM-CSF-mediated pro-inflammatory programs. Additionally, loss led decreased DCs accompanied by upregulation C/EBPβ DC progenitor populations, negatively development. ChIP-seq analysis revealed binds directly C/EBPβ’s gene locus, indicating may repress Cebpb. In contrast, did not affect macrophage development, but shift towards anti-inflammatory state. These findings demonstrate polarization. Defects either aspects could contribute lung vivo.