REVIEW article

Front. Cell. Infect. Microbiol.

Sec. Clinical Microbiology

Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1595076

This article is part of the Research TopicRecent Advancements in the Research Models of Infectious DiseasesView all 10 articles

Experimental dissection of tuberculosis protective immunity: a human perspective

Provisionally accepted
  • 1Swiss Tropical and Public Health Institute (Swiss TPH), Basel, Switzerland
  • 2University of Basel, Basel, Switzerland

The final, formatted version of the article will be published soon.

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), has plagued humankind for millennia. Claiming 1.25 million lives in 2023, TB remains the worldwide leading cause of death from a single-infectious agent. Improved vaccines, diagnostics and treatment regimens for drugsusceptible and drug-resistant cases are paramount to attain the goals of the WHO's End TB Strategy.Our knowledge gap in protective immunity in TB impedes the development of such new vaccines and host-directed interventions. Mtb is a pathogen highly adapted to humans and primarily infects the lungs. Access to relevant specimens is invasive, preventing ample human TB studies, which therefore mostly rely on peripheral blood specimens and biopsies. Thus, there is a need for relevant surrogates.In recent years, in vivo, in vitro, and in silico systems have arisen to approach and model different aspects of TB pathogenesis. Moving away from cell-line infections and classical animal models, TB research has advanced to genetically diverse mice, 3D organoid cultures and computational modelling.We will review current TB models and discuss their applicability to decipher protective human immunity, understand disease progression, transmission, as well as evaluate vaccine candidates and unravel host-directed therapeutic approaches.

Keywords: Tuberculosis, Immunology & Infectious Diseases, human, Model, Systems Immunology

Received: 17 Mar 2025; Accepted: 04 Jun 2025.

Copyright: © 2025 Schmidiger and Portevin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Damien Portevin, Swiss Tropical and Public Health Institute (Swiss TPH), Basel, Switzerland

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.