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NK cells are strongly activated by L assa and M opeia virus‐infected human macrophages in vitro but do not mediate virus suppression
Author(s) -
Russier Marion,
Reynard Stéphanie,
Tordo Noël,
Baize Sylvain
Publication year - 2012
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201142099
Subject(s) - biology , interleukin 21 , interleukin 12 , nk 92 , virology , lassa virus , immunology , immune system , virus , in vitro , cytotoxic t cell , t cell , biochemistry
L assa virus ( LASV ) and M opeia virus ( MOPV ) are closely related A renaviruses. LASV causes hemorrhagic fever, whereas MOPV is not pathogenic. Both viruses display tropism for APC s such as DC s and macrophages. During viral infections, NK cells are involved in the clearance of infected cells and promote optimal immune responses by interacting with APC s. We used an in vitro model of human NK and APC coculture to study the role of NK cells and to characterize their interactions with APC s during LASV and MOPV infections. As expected, NK cells alone were neither infected nor activated by LASV and MOPV , and infected DC s did not activate NK cells. By contrast, LASV ‐ and MOPV ‐infected macrophages activated NK cells, as shown by the upregulation of CD 69, NK p30, and NK p44, the downregulation of CXCR 3, and an increase in NK ‐cell proliferation. NK cells acquired enhanced cytotoxicity, as illustrated by the increase in granzyme B ( G rz B ) expression and killing of K 562 targets, but did not produce IFN ‐γ. Contact between NK cells and infected macrophages and type I IFN s were essential for activation; however, NK cells could not kill infected cells and control infection. Overall, these findings show that MOPV ‐ as well as pathogenic LASV ‐infected macrophages mediate NK ‐cell activation.