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Roles of Soluble and Membrane TNF and Related Ligands in Mycobacterial Infections: Effects of Selective and Non-selective TNF Inhibitors During Infection

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Book cover Advances in TNF Family Research

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 691))

Abstract

TNF plays an essential and non-redundant role in host defense mechanisms against Mycobacterium tuberculosis (Mtb) infection. TNF contributes to the development of granulomas, microstructures encasing pathogens and concentrating interactions between phagocytes and lymphocytes, and promotes bactericidal pathways to limit and destroy the invading intracellular pathogen. Production of TNF is associated with the development of human inflammatory diseases, and its inhibition, although an effective therapy, increases the risk of infections including either new or reactivation of tuberculosis infection. Studies on the role of membrane TNF in the absence of secreted TNF using genetic mouse models have shown that membrane TNF protects from M. bovis BCG and acute M. tuberculosis infections but does not induce inflammation in mouse. Pharmacological approaches of selective and non-selective soluble TNF inhibition show that a selective inhibitor of soluble TNF does not suppress host immunity to M. tuberculosis and M. bovis BCG infections, yet protects mice from arthritis and liver inflammatory diseases. This suggests that neutralization of soluble TNF may be effective to inhibit inflammatory diseases and also reduce the infection risks associated with current anti-TNF therapies.

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Acknowledgment

This work was supported by grants from EC (TB REACT Contract no. 028190) and FNRS (to IG).

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Authors and Affiliations

  1. Department of Pathology and Immunology, CMU, University of Geneva, Geneva, Switzerland

    Irene Garcia & Maria L. Olleros

  2. Orleans University and CNRS, Molecular Immunology and Embryology UMR6218, Orleans, France

    Valerie F.J. Quesniaux

  3. Institute of Infectious Disease and Molecular Medicine, and National Health Laboratory Service, University of Cape Town, Cape Town, South Africa

    Muazzam Jacobs & Nasiema Allie

  4. Laboratory of Molecular Immunology, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia

    Sergei A. Nedospasov

  5. German Rheumatism Research Center, Berlin, Germany

    Sergei A. Nedospasov

  6. Biotherapeutics Xencor, Inc., 111 West Lemon Avenue, Monrovia, CA, 91016, USA

    David E. Szymkowski

  7. Orleans University and CNRS, Molecular Immunology and Embryology, Orleans, France

    Bernhard Ryffel

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  1. Irene Garcia
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  2. Maria L. Olleros
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  3. Valerie F.J. Quesniaux
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  4. Muazzam Jacobs
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  5. Nasiema Allie
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  6. Sergei A. Nedospasov
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  7. David E. Szymkowski
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  8. Bernhard Ryffel
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Corresponding author

Correspondence to Irene Garcia .

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Editors and Affiliations

  1. Dept. Biological Chemistry, Weizmann Institute of Science, 1 Herzl Street, Rehovot, 76100, Israel

    David Wallach

  2. Dept. Biological Chemistry, Weizmann Institute of Science, 1 Herzl Street, Rehovot, 76100, Israel

    Andrew Kovalenko

  3. Kennedy Institute of Rheumatology, Imperial College London, Aspenlea Rd. 1, London, W6 8LH, United Kingdom

    Marc Feldmann

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Garcia, I. et al. (2011). Roles of Soluble and Membrane TNF and Related Ligands in Mycobacterial Infections: Effects of Selective and Non-selective TNF Inhibitors During Infection. In: Wallach, D., Kovalenko, A., Feldmann, M. (eds) Advances in TNF Family Research. Advances in Experimental Medicine and Biology, vol 691. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6612-4_20

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