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Alveolar macrophage immunobiology and functional genomics: Unlocking human to human variation in host response to M. tuberculosis

ABSTRACT: An innovative, high-throughput approach was proposed to identify key gene expression profiles and regulatory polymorphisms affecting innate immunity to TB by studying interactions between M.tb and human alveolar macrophages (AMs). We systematically analyzed interactions of a virulent M.tb strain with freshly isolated human AMs from 28 healthy adult donors, measuring host RNA expression and secreted candidate proteins associated with TB pathogenesis over 72h. We observed large inter-individual differences in bacterial uptake and growth, with tenfold variation in M.tb load at 72h, reflected by large variation of gene expression programs. Systems analysis of differential and variable RNA and protein expression identifies TB-associated genes and networks (e.g., IL1B and IDO1). RNA time profiles document early stimulation of M1-type macrophage gene expression followed by emergence of an M2-type profile.

ORGANISM(S): Homo sapiens

PROVIDER: GSE189996 | GEO | 2023/08/07

REPOSITORIES: GEO

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