Kirimanjeswara Girish S, Mann Paul B, Pilione Mylisa, Kennett Mary J, Harvill Eric T
Immunology Research Laboratories, Department of Biomedical Veterinary Sciences, Pennsylvania State University, University Park 16802, USA.
J Immunol. 2005 Dec 1;175(11):7504-11. doi: 10.4049/jimmunol.175.11.7504.
Although the antibacterial effects of Abs are well studied in in vitro systems, the in vivo effects of Abs cannot always be accurately predicted. Complicated cross-talk between different effector functions of Abs and various arms of the immune system can affect their activities in vivo. Using the mouse respiratory pathogen Bordetella bronchiseptica, we examined the mechanisms of Ab-mediated clearance of bacteria from the respiratory tract. Interestingly, although TLR4 was not necessary for protective immunity following infection, it was required for rapid bacterial clearance in mice that were vaccinated or adoptively transferred Abs. TLR4 was important for the rapid recruitment of neutrophils that are necessary for Ab-mediated bacterial clearance via a mechanism that requires both FcgammaR and CR3. These data are consistent with a model in which TLR4-mediated inflammatory responses aid in the recruitment of neutrophils, which phagocytose Ab- and complement-opsonized bacteria via FcgammaRs and CR3. Although pattern recognition receptors are known to be involved in innate immunity and the generation of adaptive immunity, their contributions to specific adaptive immune functions should be considered in ongoing efforts to improve vaccine-induced protective immunity.
尽管抗体(Abs)的抗菌作用在体外系统中已得到充分研究,但抗体在体内的作用并不能总是被准确预测。抗体的不同效应功能与免疫系统的各个分支之间复杂的相互作用会影响它们在体内的活性。我们使用小鼠呼吸道病原体支气管败血博德特氏菌,研究了抗体介导的呼吸道细菌清除机制。有趣的是,尽管感染后保护性免疫不需要Toll样受体4(TLR4),但在接种疫苗或接受过继转移抗体的小鼠中,快速清除细菌需要TLR4。TLR4对于通过一种既需要FcγR又需要补体受体3(CR3)的机制快速募集抗体介导的细菌清除所必需的中性粒细胞很重要。这些数据与一个模型一致,即TLR4介导的炎症反应有助于中性粒细胞的募集,中性粒细胞通过FcγR和CR3吞噬抗体和补体调理的细菌。尽管已知模式识别受体参与固有免疫和适应性免疫的产生,但在不断努力提高疫苗诱导的保护性免疫的过程中,应考虑它们对特定适应性免疫功能的贡献。