| First Author | Nishikawa F | Year | 1998 |
| Journal | Immunology | Volume | 95 |
| Issue | 4 | Pages | 640-7 |
| PubMed ID | 9893057 | Mgi Jnum | J:52336 |
| Mgi Id | MGI:1328877 | Doi | 10.1046/j.1365-2567.1998.00647.x |
| Citation | Nishikawa F, et al. (1998) The full expression of the ity phenotype in ityr mice requires C3 activation by Salmonella lipopolysaccharide. Immunology 95(4):640-7 |
| abstractText | Our previous study has shown that the rapid and sufficient activation of complement by Salmonella lipopolysaccharide occurs in genetically resistant (Ity(r)) A/J mice. To assess whether the level of complement activation by a virulent strain of Salmonella typhimurium regulates the level of murine natural resistance, we compared levels of serum complement activation by S. Typhimurium and kinetics of serum-opsonized S. Typhimurium grown in macrophages using several strains of resistant (Ity(r)) and susceptible (Ity(s)) mice. Ity(s) macrophages killed intracellular S. Typhimurium to the same extent as did Ity(r) macrophages when the pathogen was opsonized with Ity(r) serum. Opsonization of S. Typhimurium with Ity(s) serum reduced intracellular killing activity in Ity(r) macrophages to the same level as seen with Ity(s) macrophages. Incubation of S. Typhimurium with 25% Mg2+ EGTA (5 mM MgCl2-3 mM ethylene glycol-bis (beta-aminotheyl either)-N,N,N',N'-tetraacetic acid)-chelated Ity(r) serum resulted in higher levels of C3 deposition onto the surface of this bacteria, C3b generation and also C3 consumption, compared with that with Mg2+ EGTA-chelated Ity(s) serum. Opsonization of S. Typhimurium with A/J serum prior to infection increased early resistance in Ity(s) mice. Infection with a virulent strain of S. Typhimurium induced the expression of interleukin-10 (IL- 10) mRNA at higher levels in C57BL/6 mice than in A/J mice. However, opsonization of S. Typhimurium with A/J serum decreased bacterial growth in the spleen of C57BL/6 mice to the same level as observed for A/J mice in association with decreased expression levels of IL-IO mRNA. Moreover, administration of anti-C3 antibodies reduced the resistance of A/J mice in association with a decrease in serum levels of C3. These results indicate that the high level of complement activation via the alternative pathway in Ity(r) serum by a virulent strain of S. Typhimurium reduces the virulence of this pathogen, which may contribute to the full expression of Ity phenotype in Ity(r) mice. |
