Open Access

REVIEW

Review: Reactivation of tuberculosis by tumor necrosis factor neutralization

Muazzam Jacobs¹, Arina Samarina², Sergei Grivennikov^2,3, Tania Botha⁴, Nasiema Allie¹, Cecile Fremond², Dieudonnée Togbe², Virginie Vasseur², Stephanie Rose², Francois Erard², Analbery Monteiro², Sergei Nedospasov^3,5, Valerie Quesniaux², Bernhard Ryffel^1,2

1 Institute of Infectious Disease and Molecular Medicine, IIDMM, University of Cape Town, RSA
2 Centre National de la Recherche Scientifique, UMR6218 and University, Orleans, France
3 Laboratory of Molecular Immunology, Engelhardt Institute of Molecular Biology, Russian. Please verify this affiliation Academy of Sciences, 32 Vavilov Str., 119991, Moscow, Russia
4 Cape Peninsula University of Technology, Cape Town, RSA
5 Max Planck Institute, Immunobiology, Berlin, Germany

* Corresponding Author: B. Ryffel,

European Cytokine Network 2007, 18(1), 1-9. https://doi.org/10.1684/ecn.2007.0083

Abstract

Tumor necrosis factor (TNF) is required in the control of infection with Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis. TNF is essential and non-redundant for forming microbiocidal granulomas, and cannot be replaced by other members of the TNF family. We established a model of latent Mtb infection in mice, allowing investigation of the reactivation of latent Mtb as observed in patients receiving TNF-neutralizing therapy used in rheumatoid arthritis and Crohn’s disease. Antibody neutralization of TNF is able to reactivate clinically silent Mtb infection. Using mutant mice expressing solely membrane, but not soluble TNF, we demonstrated that membrane TNF is sufficient to control acute Mtb infection. Therefore, we hypothesize that TNF-neutralizing therapy, sparing membrane TNF, may have an advantage as compared to complete neutralization. In conclusion, endogenous TNF is critical for the control of tuberculosis infection. Genetic absence or pharmacological neutralization of TNF results in uncontrolled infection, while selective neutralization might retain the desired anti-inflammatory effect but reduce the infectious risk.

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