CD69 Deficiency Enhances the Host Response to Vaccinia Virus Infection through Altered NK Cell Homeostasis.

Details

Serval ID
serval:BIB_C2CE7EC01BDD
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
CD69 Deficiency Enhances the Host Response to Vaccinia Virus Infection through Altered NK Cell Homeostasis.
Journal
Journal of virology
Author(s)
Notario L., Alari-Pahissa E., de Molina A., Lauzurica P.
ISSN
1098-5514 (Electronic)
ISSN-L
0022-538X
Publication state
Published
Issued date
15/07/2016
Peer-reviewed
Oui
Volume
90
Number
14
Pages
6464-6474
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
During the host response to viral infection, the transmembrane CD69 protein is highly upregulated in all immune cells. We have studied the role of CD69 in the murine immune response to vaccinia virus (VACV) infection, and we report that the absence of CD69 enhances protection against VACV at both short and long times postinfection in immunocompetent and immunodeficient mice. Natural killer (NK) cells were implicated in the increased infection control, since the differences were greatly diminished when NK cells were depleted. This role of NK cells was not based on an altered NK cell reactivity, since CD69 did not affect the NK cell activation threshold in response to major histocompatibility complex class I NK cell targets or protein kinase C activation. Instead, NK cell numbers were increased in the spleen and peritoneum of CD69-deficient infected mice. That was not just secondary to better infection control in CD69-deficient mice, since NK cell numbers in the spleens and the blood of uninfected CD69(-/-) mice were already augmented. CD69-deficient NK cells from infected mice did not have an altered proliferation capacity. However, a lower spontaneous cell death rate was observed for CD69(-/-) lymphocytes. Thus, our results suggest that CD69 limits the innate immune response to VACV infection at least in part through cell homeostatic survival.
We show that increased natural killer (NK) cell numbers augment the host response and survival after infection with vaccinia virus. This phenotype is found in the absence of CD69 in immunocompetent and immunodeficient hosts. As part of the innate immune system, NK lymphocytes are activated and participate in the defense against infection. Several studies have focused on the contribution of NK cells to protection against infection with vaccinia virus. In this study, it was demonstrated that the augmented early NK cell response in the absence of CD69 is responsible for the increased protection seen during infection with vaccinia virus even at late times of infection. This work indicates that the CD69 molecule may be a target of therapy to augment the response to poxvirus infection.

Keywords
Animals, Antigens, CD/physiology, Antigens, Differentiation, T-Lymphocyte/physiology, Female, Homeostasis, Immunity, Innate/immunology, Killer Cells, Natural/immunology, Killer Cells, Natural/metabolism, Killer Cells, Natural/pathology, Lectins, C-Type/physiology, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Peritoneum/immunology, Spleen/immunology, Vaccinia/immunology, Vaccinia/virology, Vaccinia virus/immunology
Pubmed
Open Access
Yes
Create date
29/05/2016 15:32
Last modification date
20/08/2019 16:37
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