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*
Department of Pathology, and
Division of Infectious Diseases, Case Western Reserve University, Cleveland, OH 44106; and
Department of Internal Medicine, University of Iowa, Iowa City, IA 52242
Unmethylated CpG motifs in bacterial DNA or short
oligodeoxynucleotides (ODN) stimulate cells of the immune system and
provide adjuvant activity. CpG DNA directly activates macrophages to
secrete IL-12 and TNF-
and increases transcription of various genes,
but its effects on macrophage Ag processing remain uncertain. The
effects of CpG ODN on class II MHC (MHC-II) Ag processing and
presentation were examined using peritoneal macrophages that were
cultured for 18 h with CpG ODN and then pulsed with protein Ags. T
cell hybridomas were used to detect presentation of specific
peptide:MHC-II complexes. Both CpG ODN and LPS inhibited processing of
bovine RNase and hen egg lysozyme. Presentation of exogenous peptides
was inhibited to a lesser degree. Treatment of macrophages for 18
h with CpG ODN decreased surface MHC-II expression, as measured by flow
cytometry. Furthermore, Northern blot analysis revealed that treatment
with CpG ODN decreased I-Ak mRNA. Endocytosis by
macrophages, as measured by uptake of fluorescent dextran, was not
altered by treatment with CpG ODN. The inhibitory effect of CpG ODN on
Ag processing was seen after prolonged (18 h) treatment of macrophages,
but not after short treatment (e.g., 2 h) with CpG ODN and protein
Ag. Enhancement of macrophage Ag processing was not seen at any time
point of CpG ODN exposure, in contrast to data from other studies with
dendritic cells. In summary, exposure of macrophages to CpG ODN results
in a decrease in macrophage Ag processing and presentation, which is
largely mediated by a decrease in synthesis of MHC-II
molecules.
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