Measles virus nucleoprotein induces a regulatory immune response and reduces atherosclerosis in mice.
BACKGROUND
Recent studies clearly suggest that regulatory T cells play a critical role in the control of the immunoinflammatory response in atherosclerosis and substantially limit lesion development. Measles virus infection or vaccination is associated with immune depression, in part through the induction of an antiinflammatory response by measles virus nucleoprotein. We hypothesized that the antiinflammatory properties of measles virus nucleoprotein may limit the development atherosclerosis.


RESULTS
Here, we show for the first time that repetitive administration of measles virus nucleoprotein to apolipoprotein E-deficient mice promotes an antiinflammatory T-regulatory-cell type 1-like response and inhibits macrophage and T-cell accumulation within the lesions. Treatment with measles virus nucleoprotein significantly reduces the development of new atherosclerotic plaques and markedly inhibits the progression of established lesions. The antiatherosclerotic potential of nucleoprotein is retained in its short N-terminal segment. The protective effects on lesion size are lost in mice with lymphocyte deficiency.


CONCLUSIONS
Our findings identify a novel mechanism of immune modulation by measles virus nucleoprotein through the promotion of a regulatory T-cell response and suggest that this property may be harnessed for treating atherosclerosis, the first cause of heart disease and stroke.
Ait-Oufella
Hafid
H
Inserm U689, Centre de Recherche Cardiovasculaire Lariboisière, Hôpital Lariboisière, 41, Bd de la Chapelle, 75010 Paris, France.
Horvat
Branka
B
Kerdiles
Yann
Y
Herbin
Olivier
O
Gourdy
Pierre
P
Khallou-Laschet
Jamila
J
Merval
Régine
R
Esposito
Bruno
B
Tedgui
Alain
A
Mallat
Ziad
Z
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000276:immunology* / Q000517:prevention & control*; D016367:Baculoviridae; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D005822:Genetic Vectors; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control; D008297:Male; D008459:Measles virus / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009698:Nucleoproteins / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use
D001057:Apolipoproteins E; D009698:Nucleoproteins; D011994:Recombinant Proteins; D014764:Viral Proteins