Cebron Nathan, Maman Sarah, Walachowski Sarah, Gausserès Blandine, Cunha Patricia, Rainard Pascal, Foucras Gilles
IHAP, Université de Toulouse, ENVT, INRAE, 31076, Toulouse, France.
SIGENAE, GenPhySE, Université de Toulouse, INRAE, INPT, ENVT, 31326, Castanet Tolosan, France.
NPJ Vaccines. 2020 Nov 24;5(1):108. doi: 10.1038/s41541-020-00258-4.
Vaccination against bovine mastitis lags behind despite high demand from the dairy industry and margin for efficacy improvement. We previously compared two immunization protocols against E. coli using either only the intramuscular route or a combination of intramuscular and mammary ductal routes, also known as 'prime and pull' strategy. A homologous mammary challenge during the memory phase showed that immunization favorably modified the mastitis course, notably in locally immunized cows in comparison to intramuscular and control adjuvant-only groups. Here, we performed whole-blood profiling through RNA-seq transcriptome and plasma cytokine 15-plex analyses at time points of the E. coli mastitis that showed significant clinical and laboratory differences among the groups. Diminished production of inflammatory cytokines and increased IFNγ were detected in the blood of immunized cows, where a T lymphocyte activation profile was evidenced at 12-h post infection. Acute phase neutropenia was less severe in these cows, and pathways related to neutrophil diapedesis and monocyte activation were also present. Furthermore, three intramammary-immunized cows showing faster healing and shorter mastitis duration had gene profiles that differed from their counterparts, but without any clue for the mastitis susceptibility difference. Inasmuch, when gene expression of CD4 T cells was assessed in mammary tissue, enrichment of IL-17-associated pathways was identified in the quarters of intramammary-immunized cows not only after challenge but also in the control quarters that were not infected. These findings indicate that local immunization mobilizes protective mechanisms that rely on the settlement of type 3 immunity-related CD4 T cells prior to infection.
尽管乳业有很高的需求且在提高疫苗效力方面有空间，但针对牛乳腺炎的疫苗接种仍滞后。我们之前比较了两种针对大肠杆菌的免疫方案，一种仅采用肌肉注射途径，另一种采用肌肉注射和乳腺导管途径相结合的方式，即所谓的“初免和激发”策略。在记忆阶段进行的同源乳腺攻毒显示，免疫能有利地改变乳腺炎病程，特别是与肌肉注射组和仅使用佐剂的对照组相比，局部免疫的奶牛表现更为明显。在此，我们在大肠杆菌乳腺炎的时间点通过RNA测序转录组和血浆细胞因子15重分析进行全血分析，结果显示各组之间在临床和实验室方面存在显著差异。在免疫奶牛的血液中检测到炎症细胞因子的产生减少且IFNγ增加，在感染后12小时有T淋巴细胞活化特征。这些奶牛的急性期中性粒细胞减少症不那么严重，并且还存在与中性粒细胞渗出和单核细胞活化相关的途径。此外，三头乳腺内免疫的奶牛愈合更快且乳腺炎持续时间更短，它们的基因图谱与其他奶牛不同，但没有任何线索表明存在乳腺炎易感性差异。同样，当在乳腺组织中评估CD4 T细胞的基因表达时，不仅在攻毒后，而且在未感染的对照乳腺中，在乳腺内免疫奶牛的乳腺中都发现了IL-17相关途径的富集。这些发现表明，局部免疫调动了在感染前依赖3型免疫相关CD4 T细胞定居的保护机制。
