RT Journal Article
SR Electronic
T1 Exaggerated in vivo IL-17 responses discriminate recall responses in active TB
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 516690
DO 10.1101/516690
A1 Gabriele Pollara
A1 Carolin T Turner
A1 Gillian S Tomlinson
A1 Lucy CK Bell
A1 Ayesha Khan
A1 Luis Felipe Peralta
A1 Anna Folino
A1 Ayse Akarca
A1 Cristina Venturini
A1 Tina Baker
A1 Fabio LM Ricciardolo
A1 Teresa Marafioti
A1 Cesar Ugarte-Gil
A1 David AJ Moore
A1 Benjamin M Chain
A1 Mahdad Noursadeghi
YR 2020
UL http://biorxiv.org/content/early/2020/07/31/516690.abstract
AB 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. Interferon gamma (IFNγ) responses do not discriminate between protection and pathogenicity, but IL-17A/F responses, known to drive pathology in diverse chronic inflammatory diseases, have also been associated with TB pathogenesis in animal models. At the site of in vivo immune recall responses to Mtb modelled by the tuberculin skin test, we show for the first time that active TB in humans is also associated with exaggerated IL-17A/F expression, accumulation of Th17 cells and IL-17A/F bioactivity, including increased neutrophil recruitment and matrix metalloproteinase-1 expression directly implicated in TB pathogenesis. These features discriminate recall responses in patients with active TB from those with cured or latent infection and are also evident at the site of TB disease. Our data support targeting of this pathway in host-directed therapy for TB.Competing Interest StatementThe authors have declared no competing interest.