IFN-alpha-mediated increase in cytolytic activity of maturing NK cell upon exposure to HSV-infected myelomonocytes.

Abstract:

:Impaired control of chronic pathogen replication may be associated to alterations of NK-cell function. Whether mechanisms underlying this dysfunction involve perturbations of differentiating NK cells is still unknown. We studied an "in vitro" model of differentiation from CD34(+)Lin(-) precursors growing only myelomonocytes and maturing NK cells and where myelomonocytes could be suitably infected with HSV, HIV, or vaccinia. Cultures were evaluated by cytofluorometry and cytotoxicity assays for perturbations in differentiating NK cells. Increased expression of natural cytotoxicity receptors on maturing NK cells with increased cytolytic activity was observed with HSV-1 infection, and with vaccinia while no modulation of NK-cell phenotype nor cytotoxic activity were evident with an ssRNA lentivirus (HIV-1). In the presence of constant IL-12 and IL-15 concentrations, the observed effect did not require cell contact, involved IFN-alpha and was not reproduced by the addition of TLR9 agonist, nor blocked by TLR9 antagonists. Virus replication at sites of NK-cell precursor development may have different outcomes depending on the interaction between invading viruses and maturing NK cells. Thus, NK-cell precursors may be involved in the immune response to dsDNA viruses and possibly contribute to efficient control of virus infection.

journal_name

Eur J Immunol

authors

Costa P,Sivori S,Bozzano F,Martini I,Moretta A,Moretta L,De Maria A

doi

10.1002/eji.200838532

subject

Has Abstract

pub_date

2009-01-01 00:00:00

pages

147-58

issue

1

eissn

0014-2980

issn

1521-4141

journal_volume

39

pub_type

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