US Food and Drug Administration, National Center for Toxicological Research, Division of Microbiology, Jefferson, AR 72079, USA.
Benef Microbes. 2012 Mar 1;3(1):33-42. doi: 10.3920/BM2011.0041.
Probiotic lactic acid bacteria (LAB) have been shown to alleviate inflammation, enhance the immunogenicity of rotavirus vaccines, or reduce the severity of rotavirus diarrhoea. Although the mechanisms are not clear, the differential Th1/Th2/Th3-driving capacities and modulating effects on cytokine production of different LAB strains may be the key. Our goal was to delineate the influence of combining two probiotic strains of Lactobacillus acidophilus and Lactobacillus reuteri on the development of cytokine responses in neonatal gnotobiotic pigs infected with human rotavirus (HRV). We demonstrated that HRV alone, or HRV plus LAB, but not LAB alone, initiated serum cytokine responses, as indicated by significantly higher concentrations of IFN-α, IFN-γ, IL-12, and IL-10 at postinoculation day (PID) 2 in the HRV only and LAB+HRV+ pigs compared to LAB only and LAB-HRV- pigs. Peak cytokine responses coincided with the peak of HRV replication. LAB further enhanced the Th1 and Th2 cytokine responses to HRV infection as indicated by significantly higher concentrations of IL-12, IFN-γ, IL-4 and IL-10 in the LAB+HRV+ pigs compared to the LAB-HRV+ pigs. The LAB+HRV+ pigs maintained relatively constant concentrations of TGF-β compared to the HRV only group which had a significant increase at PID 2 and decrease at PID 7, suggesting a regulatory role of LAB in maintaining gut homeostasis. At PID 28, cytokine secreting cell (CSC) responses, measured by ELISpot, showed increased Th1 (IL-12, IFN-γ) CSC numbers in the LAB+HRV+ and LAB-HRV+ groups compared to LAB only and LAB-HRV- pigs, with significantly increased IL-12 CSCs in spleen and PBMCs and IFN-γ CSCs in spleen of the LAB+HRV+ group. Thus, HRV infection alone, but not LAB alone was effective in inducing cytokine responses but LAB significantly enhanced both Th1 and Th2 cytokines in HRV-infected pigs. LAB may also help to maintain immunological homeostasis during HRV infection by regulating TGF-β production.
已证实益生菌乳酸杆菌（LAB）可减轻炎症，增强轮状病毒疫苗的免疫原性，或减轻轮状病毒腹泻的严重程度。尽管其机制尚不清楚，但不同 LAB 菌株的差异 Th1/Th2/Th3 驱动能力和对细胞因子产生的调节作用可能是关键。我们的目标是描述将两种益生菌嗜酸乳杆菌和罗伊氏乳杆菌的菌株联合使用对感染人轮状病毒（HRV）的新生无菌猪细胞因子反应发展的影响。我们证明，仅 HRV、或 HRV 加 LAB，但不是单独的 LAB，即可引发血清细胞因子反应，与仅 LAB 和 LAB-HRV-猪相比，仅 HRV 和 LAB+HRV+猪在接种后第 2 天（PID）时 IFN-α、IFN-γ、IL-12 和 IL-10 的浓度明显更高。细胞因子反应的峰值与 HRV 复制的峰值相吻合。LAB 进一步增强了对 HRV 感染的 Th1 和 Th2 细胞因子反应，与 LAB-HRV+猪相比，LAB+HRV+猪中 IL-12、IFN-γ、IL-4 和 IL-10 的浓度明显更高。与仅 HRV 组相比，LAB+HRV+猪中 TGF-β 的浓度相对恒定，而仅 HRV 组在 PID 2 时有明显增加，在 PID 7 时则减少，这表明 LAB 在维持肠道内稳态方面具有调节作用。在 PID 28 时，通过 ELISpot 测量的细胞因子分泌细胞（CSC）反应显示，与仅 LAB 和 LAB-HRV-猪相比，LAB+HRV+和 LAB-HRV+猪的 Th1（IL-12、IFN-γ）CSC 数量增加，且 LAB+HRV+猪的脾和 PBMC 中 IL-12 CSC 以及脾中 IFN-γ CSC 显著增加。因此，仅 HRV 感染而不是单独的 LAB 即可有效诱导细胞因子反应，但 LAB 可显著增强感染 HRV 的猪的 Th1 和 Th2 细胞因子。LAB 还可通过调节 TGF-β 的产生，帮助维持 HRV 感染期间的免疫内稳态。
