VanCott J L, Chatfield S N, Roberts M, Hone D M, Hohmann E L, Pascual D W, Yamamoto M, Kiyono H, McGhee J R
Children's Hospital Medical Center, Division of Infectious Disease, Cincinnati, Ohio 45229, USA.
Nat Med. 1998 Nov;4(11):1247-52. doi: 10.1038/3227.
Modifying bacterial virulence genes to probe the nature of host immunity is mostly unexplored. Here we investigate whether host immune responses can be regulated by modification of bacterial virulence genes. In mice, attenuated Salmonella mutant strains with clinical relevance elicited differential host immune responses. Oral administration of a mutant strain with a PhoP-null phenotype promoted potent innate immune responses of macrophages that were sufficient for host defense. In contrast, administration of an Aro- mutant strain elicited stronger specific antibody and T-helper (Th)-cell responses, wherein Th1-type cells were required for clearance. Thus, genetic manipulation of bacteria may be used to broadly alter immune mechanisms that regulate attenuation within the host and to tailor host immunity to specific bacterial pathogens.
通过修饰细菌毒力基因来探究宿主免疫本质的研究大多尚未开展。在此，我们研究宿主免疫反应是否可通过修饰细菌毒力基因来调控。在小鼠中，具有临床相关性的减毒沙门氏菌突变株引发了不同的宿主免疫反应。口服具有PhoP缺失表型的突变株可促进巨噬细胞强大的固有免疫反应，足以实现宿主防御。相比之下，给予Aro-突变株则引发更强的特异性抗体和辅助性T（Th）细胞反应，其中清除病原体需要Th1型细胞。因此，对细菌进行基因操作可广泛改变调节宿主体内减毒的免疫机制，并使宿主免疫适应特定的细菌病原体。
