Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, Missouri, USA.
Infect Immun. 2013 Jun;81(6):2112-22. doi: 10.1128/IAI.00297-13. Epub 2013 Apr 1.
To further understand the mechanisms of formalin-inactivated Coxiella burnetii phase I (PI) vaccine (PIV)-induced protection, we examined if B cell, T cell, CD4(+) T cell, or CD8(+) T cell deficiency in mice significantly affects the ability of PIV to confer protection against a C. burnetii infection. Interestingly, compared to wild-type (WT) mice, PIV conferred comparable levels of protection in CD4(+) T cell- or CD8(+) T cell-deficient mice and partial protection in T cell-deficient mice but did not provide measurable protection in B cell-deficient mice. These results suggest that PIV-induced protection depends on B cells. In addition, anti-PI-specific IgM was the major detectable antibody (Ab) in immune sera from PIV-vaccinated CD4(+) T cell-deficient mice, and passive transfer of immune sera from PIV-vaccinated CD4(+) T cell-deficient mice conferred significant protection. These results suggest that T cell-independent anti-PI-specific IgM may contribute to PIV-induced protection. Our results also suggested that PIV-induced protection may not depend on complement activation and Fc receptor-mediated effector functions. Furthermore, our results demonstrated that both IgM and IgG from PIV-vaccinated WT mouse sera were able to inhibit C. burnetii infection in vivo, but only IgM from PIV-vaccinated CD4(+) T cell-deficient mouse sera inhibited C. burnetii infection. Collectively, these findings suggest that PIV-induced protection depends on B cells to produce protective IgM and IgG and that T cell-independent anti-PI-specific IgM may play a critical role in PIV-induced protection against C. burnetii infection.
为了进一步了解福尔马林灭活的贝氏柯克斯体相 I（PI）疫苗（PIV）诱导保护的机制，我们研究了 B 细胞、T 细胞、CD4(+) T 细胞或 CD8(+) T 细胞缺陷是否会显著影响 PIV 赋予对贝氏柯克斯体感染的保护能力。有趣的是，与野生型（WT）小鼠相比，PIV 在 CD4(+) T 细胞或 CD8(+) T 细胞缺陷小鼠中赋予相当水平的保护，在 T 细胞缺陷小鼠中赋予部分保护，但在 B 细胞缺陷小鼠中未提供可测量的保护。这些结果表明 PIV 诱导的保护依赖于 B 细胞。此外，抗 PI 特异性 IgM 是 PIV 疫苗接种的 CD4(+) T 细胞缺陷小鼠免疫血清中主要可检测的抗体（Ab），从 PIV 疫苗接种的 CD4(+) T 细胞缺陷小鼠被动转移免疫血清可提供显著的保护。这些结果表明 T 细胞非依赖性抗 PI 特异性 IgM 可能有助于 PIV 诱导的保护。我们的结果还表明，PIV 诱导的保护可能不依赖于补体激活和 Fc 受体介导的效应功能。此外，我们的结果表明，来自 PIV 疫苗接种的 WT 小鼠血清的 IgM 和 IgG 都能够抑制体内的贝氏柯克斯体感染，但只有来自 PIV 疫苗接种的 CD4(+) T 细胞缺陷小鼠血清的 IgM 抑制贝氏柯克斯体感染。总之，这些发现表明 PIV 诱导的保护依赖于 B 细胞产生保护性 IgM 和 IgG，并且 T 细胞非依赖性抗 PI 特异性 IgM 可能在 PIV 诱导的抗贝氏柯克斯体感染的保护中发挥关键作用。
