Barker Jason H, McCaffrey Ramona L, Baman Nicki K, Allen Lee-Ann H, Weiss Jerrold P, Nauseef William M
Inflammation Program and Department of Medicine, Veterans Affairs Medical Center and the University of Iowa, Coralville, IA 52241, USA.
Microbes Infect. 2009 Jul-Aug;11(8-9):762-9. doi: 10.1016/j.micinf.2009.04.016. Epub 2009 May 4.
The remarkable infectiousness of Francisella tularensis suggests that the bacterium efficiently evades innate immune responses that typically protect the host during its continuous exposure to environmental and commensal microbes. In our studies of the innate immune response to F. tularensis, we have observed that, unlike the live vaccine strain (LVS) of F. tularensis subsp. holarctica, F. tularensis subsp. novicida U112 opsonized in pooled human serum activated the NADPH oxidase when incubated with human neutrophils. Given previous observations that F. tularensis fixes relatively small quantities of complement component C3 during incubation in human serum and the importance of C3 to neutrophil phagocytosis, we hypothesized that F. tularensis subsp. novicida may fix C3 in human serum more readily than would LVS. We now report that F. tularensis subsp. novicida fixed approximately six-fold more C3 than did LVS when incubated in 50% pooled human serum and that this complement opsonization was antibody-mediated. Furthermore, antibody-mediated C3 deposition enhanced bacterial uptake and was indispensable for the neutrophil oxidative response to F. tularensis subsp. novicida. Taken together, our results reveal important differences between these two strains of F. tularensis and may, in part, explain the low virulence of F. tularensis subsp. novicida for humans.
土拉弗朗西斯菌具有显著的传染性，这表明该细菌能有效逃避先天免疫反应，而在宿主持续接触环境微生物和共生微生物期间，先天免疫反应通常会保护宿主。在我们对土拉弗朗西斯菌先天免疫反应的研究中，我们观察到，与土拉弗朗西斯菌亚种全北区的活疫苗株（LVS）不同，在人混合血清中调理的土拉弗朗西斯菌亚种新凶手亚种U112与人中性粒细胞孵育时会激活NADPH氧化酶。鉴于之前的观察结果，即土拉弗朗西斯菌在人血清中孵育期间固定的补体成分C3相对较少，以及C3对中性粒细胞吞噬作用的重要性，我们推测土拉弗朗西斯菌亚种新凶手亚种在人血清中可能比LVS更容易固定C3。我们现在报告，当在50%人混合血清中孵育时，土拉弗朗西斯菌亚种新凶手亚种固定的C3比LVS多约六倍，并且这种补体调理作用是抗体介导的。此外，抗体介导的C3沉积增强了细菌摄取，并且对于中性粒细胞对土拉弗朗西斯菌亚种新凶手亚种的氧化反应是必不可少的。综上所述，我们的结果揭示了这两种土拉弗朗西斯菌菌株之间的重要差异，并且可能部分解释了土拉弗朗西斯菌亚种新凶手亚种对人类的低毒力。
