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Contribution of transmembrane tumor necrosis factor to host defense against Mycobacterium bovis bacillus Calmette-guerin and Mycobacterium tuberculosis infections.

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dc.contributor.authorOlleros, Maria L
dc.contributor.authorGuler, Reto
dc.contributor.authorVesin, Dominique
dc.contributor.authorParapanov, Roumen
dc.contributor.authorMarchal, Gilles
dc.contributor.authorMartinez-Soria, Eduardo
dc.contributor.authorCorazza, Nadia
dc.contributor.authorPache, Jean-Claude
dc.contributor.authorMüller, Christoph
dc.contributor.authorGarcia, Irene
dc.date.accessioned2024-10-11T17:16:17Z
dc.date.available2024-10-11T17:16:17Z
dc.date.issued2005-04
dc.description.abstractTo study the specific role of transmembrane tumor necrosis factor (TmTNF) in host defense mechanisms against bacillus Calmette-Guerin (BCG) and Mycobacterium tuberculosis infections, we compared the immune responses of TNF/lymphotoxin (LT)-alpha(-/-) mice expressing a noncleavable transgenic TmTNF (TmTNF tg) to those of TNF/LT-alpha(-/-) and wild-type mice. Susceptibility of TNF/LT-alpha(-/-) mice to BCG infection was associated with impaired induction of systemic RANTES but not of monocyte chemoattractant protein 1 (MCP-1), the development of excessive local and systemic Th1-type immune responses, and a substantially reduced inducible nitric oxide synthase (iNOS) activity. Resistance of TmTNF tg mice to BCG infection was associated with efficient activation of iNOS in granulomas and with the regulated release of local and systemic chemokines and Th1-type cytokines. However, M. tuberculosis infection of TmTNF tg mice resulted in longer survival and enhanced resistance compared to TNF/LT-alpha(-/-) mice but higher sensitivity than wild-type mice. TmTNF tg mice exhibited reduced pulmonary iNOS expression and showed an exacerbated cellular infiltration in the lungs despite a modest bacillary content. Our data thus indicate a role for TmTNF in host defense against mycobacteria by contributing to induction and regulation of Th1-type cytokine and chemokine expression leading to development of bactericidal granulomas expressing iNOS, which critically determines susceptibility versus resistance of the host to mycobacterial infections.
dc.description.numberOfPages12
dc.description.sponsorshipInstitut für Pathologie
dc.identifier.doi10.48350/173180
dc.identifier.pmid15793291
dc.identifier.publisherDOI10.1016/S0002-9440(10)62331-0
dc.identifier.urihttps://boris-portal.unibe.ch/handle/20.500.12422/87649
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofAmerican journal of pathology
dc.relation.issn0002-9440
dc.relation.organizationDCD5A442BF89E17DE0405C82790C4DE2
dc.subject.ddc500 - Science::570 - Life sciences; biology
dc.subject.ddc600 - Technology::610 - Medicine & health
dc.titleContribution of transmembrane tumor necrosis factor to host defense against Mycobacterium bovis bacillus Calmette-guerin and Mycobacterium tuberculosis infections.
dc.typearticle
dspace.entity.typePublication
dspace.file.typetext
oaire.citation.endPage1120
oaire.citation.issue4
oaire.citation.startPage1109
oaire.citation.volume166
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oairecerif.author.affiliationInstitut für Pathologie
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oairecerif.author.affiliationInstitut für Pathologie
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unibe.date.licenseChanged2022-09-23 09:01:43
unibe.description.ispublishedpub
unibe.eprints.legacyId173180
unibe.journal.abbrevTitleAM J PATHOL
unibe.refereedTRUE
unibe.subtype.articlejournal

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