Dataset Information

Mycobacterium tuberculosis-dependent monocyte expression quantitative trait loci, cytokine production, and TB pathogenesis.

ABSTRACT:

Introduction

The heterogeneity of outcomes after Mycobacterium tuberculosis (Mtb) exposure is a conundrum associated with millennia of host-pathogen co-evolution. We hypothesized that human myeloid cells contain genetically encoded, Mtb-specific responses that regulate critical steps in tuberculosis (TB) pathogenesis.

Methods

We mapped genome-wide expression quantitative trait loci (eQTLs) in Mtb-infected monocytes with RNAseq from 80 Ugandan household contacts of pulmonary TB cases to identify monocyte-specific, Mtb-dependent eQTLs and their association with cytokine expression and clinical resistance to tuberculin skin test (TST) and interferon-γ release assay (IGRA) conversion.

Results

cis-eQTLs (n=1,567) were identified in Mtb-infected monocytes (FDR<0.01), including 29 eQTLs in 16 genes which were Mtb-dependent (significant for Mtb:genotype interaction [FDR<0.1], but not classified as eQTL in uninfected condition [FDR≥0.01]). A subset of eQTLs were associated with Mtb-induced cytokine expression (n=8) and/or clinical resistance to TST/IGRA conversion (n=1). Expression of BMP6, an Mtb-dependent eQTL gene, was associated with IFNB1 induction in Mtb-infected and DNA ligand-induced cells. Network and enrichment analyses identified fatty acid metabolism as a pathway associated with eQTL genes.

Discussion

These findings suggest that monocyte genes contain Mtb-dependent eQTLs, including a subset associated with cytokine expression and/or clinical resistance to TST/IGRA conversion, providing insight into immunogenetic pathways regulating susceptibility to Mtb infection and TB pathogenesis.

SUBMITTER: Hong H

PROVIDER: S-EPMC10954790 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Publications

<i>Mycobacterium tuberculosis</i>-dependent monocyte expression quantitative trait loci, cytokine production, and TB pathogenesis.

Hong Hyejeong H Dill-McFarland Kimberly A KA Simmons Jason D JD Peterson Glenna J GJ Benchek Penelope P Mayanja-Kizza Harriet H Boom W Henry WH Stein Catherine M CM Hawn Thomas R TR

Frontiers in immunology 20240307

<h4>Introduction</h4>The heterogeneity of outcomes after <i>Mycobacterium tuberculosis</i> (Mtb) exposure is a conundrum associated with millennia of host-pathogen co-evolution. We hypothesized that human myeloid cells contain genetically encoded, Mtb-specific responses that regulate critical steps in tuberculosis (TB) pathogenesis.<h4>Methods</h4>We mapped genome-wide expression quantitative trait loci (eQTLs) in Mtb-infected monocytes with RNAseq from 80 Ugandan household contacts of pulmonary ...[more]

PMID: 38515745

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