Bitsaktsis Constantine, Nandi Bisweswar, Racine Rachael, MacNamara Katherine C, Winslow Gary
Wadsworth Center, New York State Department of Health, PO Box 22002, Albany, New York 12201-2002, USA.
Infect Immun. 2007 Oct;75(10):4933-41. doi: 10.1128/IAI.00705-07. Epub 2007 Jul 30.
Although humoral immunity has been shown to contribute to host defense during intracellular bacterial infections, its role has generally been ancillary. Instead, CD4 T cells are often considered to play the dominant role in protective immunity via their production of type I cytokines. Our studies of highly pathogenic Ehrlichia bacteria isolated from Ixodes ovatus (IOE) reveal, however, that this paradigm is not always correct. Immunity to IOE infection can be induced by infection with a closely related weakly pathogenic ehrlichia, Ehrlichia muris. Type I cytokines (i.e., gamma interferon, tumor necrosis factor alpha, and interleukin-12) were not necessary for E. muris-induced immunity. In contrast, humoral immunity was essential, as shown by the fact that E. muris-infected B-cell-deficient mice were not protected from IOE challenge and because E. muris immunization was effective in CD4-, CD8-, and major histocompatibility complex (MHC) class II-deficient mice. Immunity was unlikely due to nonspecific inflammation, as prior infection with Listeria monocytogenes did not induce immunity to IOE. Antisera from both wild-type and MHC-II-deficient mice provided at least partial resistance to challenge infection, and protection could also be achieved following transfer of total, but not B-cell-depleted, splenocytes obtained from E. muris-immunized mice. The titers of class-switched antibodies in immunized CD4 T-cell- and MHC class II-deficient mice, although lower than those observed in immunized wild-type mice, were significant, indicating that E. muris can induce class switch recombination in the absence of classical T-cell-mediated help. These studies highlight a major protective role for classical T-cell-independent humoral immunity during an intracellular bacterial infection.
虽然体液免疫已被证明在细胞内细菌感染期间有助于宿主防御，但其作用通常是辅助性的。相反，CD4 T细胞通常被认为通过产生I型细胞因子在保护性免疫中起主导作用。然而，我们对从卵形硬蜱分离出的高致病性埃立克体菌（IOE）的研究表明，这种模式并不总是正确的。用密切相关的弱致病性埃立克体菌——鼠埃立克体感染可诱导对IOE感染的免疫。I型细胞因子（即γ干扰素、肿瘤坏死因子α和白细胞介素-12）对鼠埃立克体诱导的免疫并非必需。相反，体液免疫至关重要，这体现在以下事实：感染鼠埃立克体的B细胞缺陷小鼠不能抵御IOE攻击，且鼠埃立克体免疫在CD4、CD8和主要组织相容性复合体（MHC）II类缺陷小鼠中有效。免疫不太可能是由于非特异性炎症，因为先前感染单核细胞增生李斯特菌并未诱导对IOE的免疫。来自野生型和MHC-II缺陷小鼠的抗血清对攻击感染提供了至少部分抗性，从感染鼠埃立克体的小鼠获得的全脾细胞（而非B细胞耗竭的脾细胞）转移后也可实现保护。免疫的CD4 T细胞和MHC II类缺陷小鼠中类别转换抗体的滴度虽然低于免疫野生型小鼠中观察到的滴度，但仍很显著，表明鼠埃立克体可在无经典T细胞介导的帮助下诱导类别转换重组。这些研究突出了经典的非T细胞依赖性体液免疫在细胞内细菌感染期间的主要保护作用。
