Abstract
ObjectiveTo investigate the antigenic effect of a peptide containing two epitopes of Chlamydia pneumoniae (Cpn) on atherosclerotic lesion formation in mice infected with Cpn.Materials and MethodsSix-week-old Apobtm2SgyLdlrtm1Her/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 Cpn. Mice were fed a high-fat diet and infected with Cpn 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.ResultsMice immunized with the combined Cpn 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.ConclusionsAtherosclerotic lesion formation may be promoted by Cpn infection in the presence of a high-fat diet, and reduced by immunization with the combined Cpn peptide. The combined peptide has more potential than either epitope alone in reducing atherosclerotic lesion development through Treg expansion.
Highlights
Chlamydia pneumoniae (Cpn) [1] is an important human pathogen that causes atypical pneumonia and is associated with various chronic inflammatory diseases such as atherosclerosis, a major cause of cardiovascular disease and death in the Western world [2,3,4,5,6]
We investigate the effect of a linear peptide containing these two putative epitopes derived from major outer membrane protein (MOMP) and outer membrane protein 5 (Omp5) of Cpn on atherosclerotic lesion formation in Cpn-infected Apobtm2Sgy Ldlrtm1Her/J mice
Detection of Cpn Infection The MOMP of Cpn was chosen as a target for amplification in nested polymerase chain reaction (PCR) DNA from infected samples only, and produced a band of the expected size after the first PCR amplification
Summary
Chlamydia pneumoniae (Cpn) [1] is an important human pathogen that causes atypical pneumonia and is associated with various chronic inflammatory diseases such as atherosclerosis, a major cause of cardiovascular disease and death in the Western world [2,3,4,5,6]. An epitope of the major outer membrane protein (MOMP) of Cpn (AA 67–74: GDYVFDRI) and the putative outer membrane protein 5 (Omp5) of Cpn (AA 284–292: QAVANGGAI) share high homology, with two sequence locations of ApoB protein (http://web.expasy.org/sim/). ApoB protein plays a crucial role in atherosclerosis as immunization with some peptides derived from ApoB protein reduce atherosclerotic lesion in several mouse models. This molecular mimicry (share high homology) was recently demonstrated in our laboratory in which an epitope containing both sequences of AA 67–74 (GDYVFDRI) and AA 284–292 (QAVANGGAI) has an effect on atherosclerotic lesion reduction in a protein scaffold in non-infected mice with Chlamydophia [11]. We investigate the effect of a linear peptide containing these two putative epitopes derived from MOMP and Omp of Cpn on atherosclerotic lesion formation in Cpn-infected Apobtm2Sgy Ldlrtm1Her/J mice
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