Activin A levels are raised during human tuberculosis and blockade of the activin signaling axis influences murine responses to M. tuberculosis infection

CAPNETZ Study group, DZIF TB study group, Natalie E. Nieuwenhuizen, Geraldine Nouailles, Jayne S. Sutherland, Joanna Zyla, Arja H. Pasternack, Jan Heyckendorf, Björn C. Frye, Kerstin Höhne, Ulrike Zedler, Silke Bandermann, Ulrike Abu Abed, Volker Brinkmann, Birgitt Gutbier, Martin Witzenrath, Norbert Suttorp, Gernot Zissel, Christoph Lange, Olli RitvosStefan H.E. Kaufmann

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

Sammanfattning

Activin A strongly influences immune responses; yet, few studies have examined its role in infectious diseases. We measured serum activin A levels in two independent tuberculosis (TB) patient cohorts and in patients with pneumonia and sarcoidosis. Serum activin A levels were increased in TB patients compared to healthy controls, including those with positive tuberculin skin tests, and paralleled severity of disease, assessed by X-ray scores. In pneumonia patients, serum activin A levels were also raised, but in sarcoidosis patients, levels were lower. To determine whether blockade of the activin A signaling axis could play a functional role in TB, we harnessed a soluble activin type IIB receptor fused to human IgG1 Fc, ActRIIB-Fc, as a ligand trap in a murine TB model. The administration of ActRIIB-Fc to Mycobacterium tuberculosis-infected mice resulted in decreased bacterial loads and increased numbers of CD4 effector T cells and tissue-resident memory T cells in the lung. Increased frequencies of tissue-resident memory T cells corresponded with downregulated T-bet expression in lung CD4 and CD8 T cells. Altogether, the results suggest a disease-exacerbating role of ActRIIB signaling pathways. Serum activin A may be useful as a biomarker for diagnostic triage of active TB or monitoring of anti-tuberculosis therapy.

Originalspråkengelska
Artikelnummere0340823
TidskriftmBio
Volym15
Nummer3
Antal sidor21
ISSN2161-2129
DOI
StatusPublicerad - 2024
MoE-publikationstypA1 Tidskriftsartikel-refererad

Bibliografisk information

Publisher Copyright:
© 2024 Nieuwenhuizen et al.

Vetenskapsgrenar

  • 11832 Mikrobiologi och virologi
  • 1184 Genetik, utvecklingsbiologi, fysiologi

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