DOI: 10.1101/516690Jan 14, 2019Paper

Exaggerated in vivo IL-17 responses discriminate recall responses in active TB

BioRxiv : the Preprint Server for Biology
Gabriele PollaraMahdad Noursadeghi

Abstract

Background: Host immune responses at the site of Mycobacterium tuberculosis (Mtb) infection serve to contain the pathogen, but also mediate the pathogenesis of tuberculosis (TB) and onward transmission of infection. Based on the premise that active TB disease is predominantly a manifestation of immunopathology, we tested the hypothesis that immune responses at the site of host-pathogen interactions would reveal enrichment of immunopathologic responses in patients with active TB that were absent in individuals with equivalent immune memory for Mtb but without disease. Methods: In cohorts of patients with active TB and cured or latent infection, we undertook molecular profiling at the site of a tuberculin skin test to model in vivo host-pathogen interactions in Mtb infection. Genome-wide transcriptional differences were identified by differential gene expression analyses. Enrichment of immune cells and cytokine activity was derived using specific transcriptional modules. Findings were validated in independent cohorts of patients with active TB, as well as Mtb infected tissues. Results: Active TB in humans is associated with exaggerated IL-17A/F expression, accumulation of Th17 cells and IL-17A bioactivity, including increased neu...Continue Reading

Related Concepts

Gene Expression
Mycobacterium tuberculosis
Neutrophil
Mental Recall
Transcription, Genetic
Tuberculin Test
Tuberculosis
Interstitial Collagenase
Site
Disease Transmission

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