Humoral Immunity and CD4+ Th1 Cells Are Both Necessary for a Fully Protective Immune Response upon Secondary Infection with Brucella melitensis
Humoral Immunity and CD4+ Th1 Cells Are Both Necessary for a Fully Protective Immune Response upon Secondary Infection with Brucella melitensis
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DOI：
10.4049/jimmunol.1302561
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发表时间：
2014-04-15
影响因子：
4.4
通讯作者：
Muraille, Eric
中科院分区：
文献类型：
--
作者：
Vitry, Marie-Alice;Mambres, Delphine Hanot;Muraille, Eric
布鲁氏菌是引起布鲁氏菌病的胞内细菌，布鲁氏菌病是世界上最常见的人畜共患病之一。鉴于这种疾病的严重医学后果，迫切需要一种安全有效的人类疫苗。由于我们缺乏对布鲁氏菌保护性记忆反应的理解，开发这种疫苗的努力受到了阻碍。在这项研究中，我们描述了在注射热灭活或活的羊布鲁氏菌16M后，与保护性免疫记忆反应产生有关的细胞和信号通路的特征。使用一组基因缺陷的小鼠，我们证明了在二次回忆反应中，布鲁氏菌特异性体液反应和CD4(+)Th1细胞必须共同作用，以在脾中授予对羊毛虫感染的保护性免疫。体液保护性免疫是通过接种热灭活菌和活菌来诱导的，它的产生不需要T细胞、MyD88/IL-12p35信号通路或激活诱导的脱氨酶介导的同型转换。与之形成鲜明对比的是，产生记忆干扰素-伽马的CD4(+)Th1细胞的存在需要活细菌和MyD88/IL-12p35途径的作用。综上所述，我们的工作确定了几个与保护性免疫记忆密切相关的免疫标记，并可能有助于定义一种合理的策略，以获得有效的人类布鲁氏菌病疫苗。
Brucella spp are intracellular bacteria that cause brucellosis, one of the most common zoonoses in the world. Given the serious medical consequences of this disease, a safe and effective human vaccine is urgently needed. Efforts to develop this vaccine have been hampered by our lack of understanding of what constitutes a protective memory response against Brucella. In this study, we characterize the cells and signaling pathways implicated in the generation of a protective immune memory response following priming by the injection of heat-killed or live Brucella melitensis 16M. Using a panel of gene-deficient mice, we demonstrated that during a secondary recall response, both the Brucella-specific humoral response and CD4(+) Th1 cells must act together to confer protective immunity in the spleen to B. melitensis infection. Humoral protective immunity is induced by the inoculation of both heat-killed and live bacteria, and its development does not require T cells, MyD88/IL-12p35 signaling pathways, or an activation-induced deaminase-mediated isotype switch. In striking contrast, the presence of memory IFN-gamma-producing CD4(+) Th1 cells requires the administration of live bacteria and functional MyD88/IL-12p35 pathways. In summary, our work identifies several immune markers closely associated with protective immune memory and could help to define a rational strategy to obtain an effective human vaccine against brucellosis.