Membrane-bound TNF induces protective immune responses to M. bovis BCG infection: regulation of memTNF and TNF receptors comparing two memTNF molecules.

Details

Serval ID
serval:BIB_0FEFC722C7FF
Type
Article: article from journal or magazin.
Collection
Publications
Title
Membrane-bound TNF induces protective immune responses to M. bovis BCG infection: regulation of memTNF and TNF receptors comparing two memTNF molecules.
Journal
PloS one
Author(s)
Olleros M.L., Vesin D., Bisig R., Santiago-Raber M.L., Schuepbach-Mallepell S., Kollias G., Gaide O., Garcia I.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2012
Peer-reviewed
Oui
Volume
7
Number
5
Pages
e31469
Language
english
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Several activities of the transmembrane form of TNF (memTNF) in immune responses to intracellular bacterial infection have been shown to be different from those exerted by soluble TNF. Evidence is based largely on studies in transgenic mice expressing memTNF, but precise cellular mechanisms are not well defined and the importance of TNF receptor regulation is unknown. In addition, memTNF activities are defined for a particular modification of the extracellular domain of TNF but a direct comparison of different mutant memTNF molecules has not been done in vivo.
To understand the activities of memTNF we compared two commonly used mouse strains lacking soluble TNF but possessing functional and normally regulated membrane-bound TNF knockin (memTNF KI) for their capacity to generate cell-mediated immune responses and resistance to M. bovis BCG infection, and to regulate TNF receptors.
M. bovis BCG infection resulted in similar bacterial loads in one strain of memTNF KI (memTNF(Δ1-9,K11E)) and in wild-type mice, in contrast, the other strain of memTNF KI mice (memTNF(Δ1-12)) showed higher sensitivity to infection with high mortality (75%), greater bacterial load and massive lung pathology. The pattern of cytokines/chemokines, inflammatory cells, pulmonary NF-κB phosphorylation, antigen-dependent IFN-γ response, and splenic iNOS was impaired in M. bovis BCG-infected memTNF(Δ1-12) KI mice. Macrophages expressing TNFR2 were reduced but soluble TNFRs were higher in memTNF(Δ1-12) KI mice during the infection. In vitro, M. bovis BCG-induced NF-κB activation and cytokines were also decreased in memTNF(Δ1-12) KI bone marrow-derived macrophages.
Our data show that two memTNF molecules exerted very different activities upon M. bovis BCG infection resulting in protection or not to bacterial infection. These results suggest a regulatory mechanism of memTNF and TNF receptors being critical in the outcome of the infection and highlight the role of cell-bound and soluble TNFR2 in memTNF-mediated anti-microbial mechanisms.

Keywords
Animals, Bone Marrow Cells/cytology, Cell Membrane/metabolism, Chemokines/metabolism, Disease Resistance/immunology, Gene Knock-In Techniques, Interferon-gamma/immunology, Interferon-gamma/metabolism, Intracellular Space/immunology, Intracellular Space/metabolism, Intracellular Space/microbiology, Macrophages/immunology, Macrophages/metabolism, Macrophages/microbiology, Mice, Mice, Inbred C57BL, Mycobacterium bovis/immunology, Mycobacterium bovis/pathogenicity, NF-kappa B/metabolism, Nitric Oxide/metabolism, Nitric Oxide Synthase Type II/metabolism, Receptors, Tumor Necrosis Factor, Type II/chemistry, Receptors, Tumor Necrosis Factor, Type II/metabolism, Solubility, Tuberculosis/immunology, Tuberculosis/veterinary, Tumor Necrosis Factor-alpha/genetics, Tumor Necrosis Factor-alpha/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
02/11/2017 11:00
Last modification date
20/08/2019 12:36
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