Isolation and partial purification of macrophage- and dendritic cell-activating components from Mycoplasma arthritidis:: Association with organism virulence and involvement with toll-like receptor 2

被引:20
作者
Cole, BC
Mu, HH
Pennock, ND
Hasebe, A
Chan, FV
Washburn, LR
Peltier, MR
机构
[1] Univ Utah, Sch Med, Dept Internal Med, Div Rheumatol, Salt Lake City, UT 84132 USA
[2] Univ S Dakota, Dept Microbiol, Vermillion, SD 57069 USA
[3] Univ Med & Dent New Jersey, Dept Obstet Gynecol & Reprod Sci, New Brunswick, NJ USA
关键词
D O I
10.1128/IAI.73.9.6039-6047.2005
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Mycoplasma arthritidis induces toxicity, arthritis, and dermal necrosis in mice. Virulence factors include a superantigen and membrane adhesins and possibly also a bacteriophage component. Here we compare the biological properties of Triton X-114 extracts derived from avirulent and virulent M. arthtitidis strains. Macrophage cell lines and resident peritoneal macrophages were used to assess inflammatory potential as indicated by production of tumor necrosis factor alpha, interleukin-6, and/or nitric oxide. The activity resided exclusively within the hydrophobic detergent phase, was unaffected by heat treatment at 100 degrees C for 30 min, and was resistant to proteinase K digestion, suggesting involvement of a lipopeptide. Contamination of extracts with endotoxin or superantigen was excluded. Extracts of the more virulent strain had higher activity than did those of the avirulent strain. Using CHO cells expressing Toll-like receptor 2 (TLR2) or TLR4, both with transfected CD14, we showed that extracts activated these cells via TLR2 but not by TLR4. Also, macrophages from C57BL/6 TLR2(-/-) mice failed to respond to the extracts, whereas those from TLR2(+/+) cells did respond. The preparations from the virulent strain of M. arthritidis were also more potent in activating dendritic cells, as evidenced by up-regulation of major histocompatibility complex class II, CD40, B7-1, and B7-2. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and subsequent elution of gel slices revealed the presence of three active moieties which corresponded to molecular masses of approximately 24, 28, and 40 kDa. Three active components were also found by reverse-phase chromatography. We suggest that macrophage activation by M. arthritidis could play a significant role in the inflammatory response induced in the host by this organism.
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页码:6039 / 6047
页数:9
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