Immunization of <i>Chlamydia pneumoniae</i> (<i>Cpn</i>)-Infected Apob^tm2SgyLdlr^tm1Her/J Mice with a Combined Peptide of <i>Cpn</i> Significantly Reduces Atherosclerotic Lesion Development

Abstract

<div><p>Objective</p><p>To investigate the antigenic effect of a peptide containing two epitopes of <i>Chlamydia pneumoniae</i> (<i>Cpn</i>) on atherosclerotic lesion formation in mice infected with <i>Cpn</i>.</p><p>Materials and Methods</p><p>Six-week-old Apob^tm2SgyLdlr^tm1Her/J mice were immunized using a repetitive immunization multiple-sites strategy with KLH-conjugated peptides derived from the major outer membrane protein and the putative outer membrane protein 5 of <i>Cpn</i>. Mice were fed a high-fat diet and infected with <i>Cpn</i> twice during the 10-week diet period. Lesions were evaluated histologically; local and systemic immune responses were analyzed by immunohistochemistry of aorta samples and cytokine measurements in plasma samples and splenocyte supernatants.</p><p>Results</p><p>Mice immunized with the combined <i>Cpn</i> peptide showed a greater reduction in lesion size compared to mice immunized with either epitope alone [54.7% vs 39.8% or 41.72%] and was also associated with a significant decrease in lesion area in descending aortas compared with those in controls (88.9% for combined Cpn peptide, 81.9% for MOMP peptide and 75.7% for Omp5, respectively). This effect was associated with a shift in the cellular composition of plaques towards decreased inflammatory cell and increased regulatory T-cell content. Additionally, the effect was also connected with decreased secretion of proinflammatory cytokines and increased production of anti-inflammatory cytokines demonstrated in plasma and in supernatant on stimulated spleen cells.</p><p>Conclusions</p><p>Atherosclerotic lesion formation may be promoted by <i>Cpn</i> infection in the presence of a high-fat diet, and reduced by immunization with the combined <i>Cpn</i> peptide. The combined peptide has more potential than either epitope alone in reducing atherosclerotic lesion development through Treg expansion.</p></div