%0 Journal Article
%T TNF-¦Á antagonists differentially induce TGF-¦Â1-dependent resuscitation of dormant-like Mycobacterium tuberculosis
%A Ainhoa Arbu¨¦s
%A Damien Portevin
%A Dominique Brees
%A Michael Kamm¨¹ller
%A Salah-Dine Chibout
%A Todd Fox
%J -
%D 2020
%R 10.1371/journal.ppat.1008312
%X TNF-¦Á- as well as non-TNF-¦Á-targeting biologics are prescribed to treat a variety of immune-mediated inflammatory disorders. The well-documented risk of tuberculosis progression associated with anti-TNF-¦Á treatment highlighted the central role of TNF-¦Á for the maintenance of protective immunity, although the rate of tuberculosis detected among patients varies with the nature of the drug. Using a human, in-vitro granuloma model, we reproduce the increased reactivation rate of tuberculosis following exposure to Adalimumab compared to Etanercept, two TNF-¦Á-neutralizing biologics. We show that Adalimumab, because of its bivalence, specifically induces TGF-¦Â1-dependent Mycobacterium tuberculosis (Mtb) resuscitation which can be prevented by concomitant TGF-¦Â1 neutralization. Moreover, our data suggest an additional role of lymphotoxin-¦Á¨Cneutralized by Etanercept but not Adalimumab¨Cin the control of latent tuberculosis infection. Furthermore, we show that, while Secukinumab, an anti-IL-17A antibody, does not revert Mtb dormancy, the anti-IL-12-p40 antibody Ustekinumab and the recombinant IL-1RA Anakinra promote Mtb resuscitation, in line with the importance of these pathways in tuberculosis immunity
%K Mycobacterium tuberculosis
%K Granulomas
%K Resuscitation
%K Cytokines
%K T cells
%K Tuberculosis
%K Antibodies
%K Cloning
%U https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008312