Measles virus nucleoprotein induces a regulatory immune response and reduces atherosclerosis in mice.

Abstract:

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. METHODS AND 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.

journal_name

Circulation

journal_title

Circulation

authors

Ait-Oufella H,Horvat B,Kerdiles Y,Herbin O,Gourdy P,Khallou-Laschet J,Merval R,Esposito B,Tedgui A,Mallat Z

doi

10.1161/CIRCULATIONAHA.107.699470

subject

Has Abstract

pub_date

2007-10-09 00:00:00

pages

1707-13

issue

15

eissn

0009-7322

issn

1524-4539

pii

CIRCULATIONAHA.107.699470

journal_volume

116

pub_type

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