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Pivotal role of KAR...
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Sjolin, HKarolinska Institutet
(author)
Pivotal role of KARAP/DAP12 adaptor molecule in the natural killer cell-mediated resistance to murine cytomegalovirus infection
- Article/chapterEnglish2002
Publisher, publication year, extent ...
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2002-03-25
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Rockefeller University Press,2002
Numbers
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LIBRIS-ID:oai:prod.swepub.kib.ki.se:1940714
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http://kipublications.ki.se/Default.aspx?queryparsed=id:1940714URI
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https://doi.org/10.1084/jem.20011427DOI
Supplementary language notes
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Language:English
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Summary in:English
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Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Natural killer (NK) cells are major contributors to early defense against infections. Their effector functions are controlled by a balance between activating and inhibiting signals. To date, however, the involvement of NK cell activating receptors and signaling pathways in the defense against pathogens has not been extensively investigated. In mice, several NK cell activating receptors are coexpressed with and function through the immunoreceptor tyrosine-based activation motif (ITAM)-bearing molecule KARAP/DAP12. Here, we have analyzed the role of KARAP/DAP12 in the early antiviral response to murine cytomegalovirus (MCMV). In KARAP/DAP12 mutant mice bearing a nonfunctional ITAM, we found a considerable increase in viral titers in the spleen (30–40-fold) and in the liver (2–5-fold). These effects were attributed to NK cells. The formation of hepatic inflammatory foci appeared similar in wild-type and mutant mice, but the latter more frequently developed severe hepatitis with large areas of focal necrosis. Moreover, the percentage of hepatic NK cells producing interferon γ was reduced by 56 ± 22% in the absence of a functional KARAP/DAP12. This is the first study that shows a crucial role for a particular activating signaling pathway, in this case the one induced through KARAP/DAP12, in the NK cell–mediated resistance to an infection. Our results are discussed in relation to recent reports demonstrating that innate resistance to MCMV requires the presence of NK cells expressing the KARAP/DAP12-associated receptor Ly49H.
Added entries (persons, corporate bodies, meetings, titles ...)
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Tomasello, E
(author)
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Mousavi-Jazi, M
(author)
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Bartolazzi, AKarolinska Institutet
(author)
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Karre, KKarolinska Institutet
(author)
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Vivier, E
(author)
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Cerboni, C
(author)
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Karolinska Institutet
(creator_code:org_t)
Related titles
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In:The Journal of experimental medicine: Rockefeller University Press195:7, s. 825-8340022-10071540-9538
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