Pneumococcal vaccination decreases atherosclerotic lesion formation: molecular mimicry between Streptococcus pneumoniae and oxidized LDL.
During the progression of atherosclerosis, autoantibodies are induced to epitopes of oxidized low-density lipoprotein (oxLDL) and active immunization of hypercholesterolemic mice with oxLDL ameliorates atherogenesis. We unexpectedly found that many autoantibodies to oxLDL derived from 'naive' atherosclerotic mice share complete genetic and structural identity with antibodies from the classic anti-phosphorylcholine B-cell clone, T15, which protect against common infectious pathogens, including pneumococci. To investigate whether in vivo exposure to pneumococci can affect atherogenesis, we immunized Ldlr(-/-) mice with Streptococcus pneumoniae. This induced high circulating levels of oxLDL-specific IgM and a persistent expansion of oxLDL-specific T15 IgM-secreting B cells primarily in the spleen, which were cross-reactive with pneumococcal determinants. Pneumococcal immunization decreased the extent of atherosclerosis, and plasma from these mice had an enhanced capacity to block the binding of oxLDL to macrophages. These studies show molecular mimicry between epitopes of oxLDL and S. pneumoniae and indicate that these immune responses can have beneficial effects.
Divisions of Endocrinology & Metabolism, Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0682 USA.
Christoph J
CJ
Binder
Sohvi
S
Hörkkö
Asheesh
A
Dewan
Mi-Kyung
MK
Chang
Emily P
EP
Kieu
Carl S
CS
Goodyear
Peter X
PX
Shaw
Wulf
W
Palinski
Joseph L
JL
Witztum
Gregg J
GJ
Silverman
D000818:Animals; D001161:Arteriosclerosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D004036:Diet, Atherogenic; D000939:Epitopes; D006801:Humans; D007114:Immunization; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018716:Molecular Mimicry; D011135:Polysaccharides, Bacterial / Q000097:blood / Q000276:immunology; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000737:chemistry / Q000276:immunology*
D000939:Epitopes; D007075:Immunoglobulin M; D008077:Lipoproteins, LDL; D011135:Polysaccharides, Bacterial; D011973:Receptors, LDL; C099252:oxidized low density lipoprotein