Protective immunity against Helicobacter is characterized by a unique transcriptional signature
Protective immunity against Helicobacter is characterized by a unique transcriptional signature
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DOI：
10.1073/pnas.1635231100
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发表时间：
2003-10-14
影响因子：
11.1
通讯作者：
Falkow, S
中科院分区：
文献类型：
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作者：
Mueller, A;O'Rourke, J;Falkow, S
使用猫螺杆菌全细胞超声疫苗与霍乱毒素作为粘膜佐剂进行免疫，可在大多数实验室小鼠中诱导长期保护性免疫力。我们对一组免疫动物进行了基因表达谱分析和免疫组织化学分析，以更好地了解保护机制。与未受保护或对照小鼠相比，受保护动物的胃表现出显着不同的转录谱，表明疫苗接种针对适当的位点并留下分子特征。上调与保护显着相关的基因中有许多脂肪细胞特异性因子。这些包括脂肪细胞特异性细胞因子脂肪素、抵抗素和脂联素以及脂肪细胞表面标记 CD36。有趣的是，潜在的保护性 T 和 B 淋巴细胞嵌入在受保护胃周围的脂肪组织中，但在受控或未受保护的胃中却从未出现过。对受保护的胃切片进行脂肪素特异性免疫组织化学染色，进一步揭示了相邻淋巴和脂肪细胞群之间的分子串扰。我们提出了一种保护机制，涉及任一或两个淋巴细胞亚类的效应反应，以及先前未认识到的驻留淋巴细胞周围脂肪组织的旁分泌功能。
Immunization with a whole-cell sonicate vaccine of Helicobacter felis in conjunction with cholera toxin as a mucosal adjuvant induces long-term protective immunity in a majority of laboratory mice. We have combined gene expression profiling and immunohistochemical analysis on a set of immunized animals to better understand the mechanism of protection. The stomachs of protected animals exhibited a strikingly different transcriptional profile compared with those of nonprotected or control mice, indicating that vaccination targets the appropriate site and leaves a molecular signature. Among the genes whose up-regulation is significantly correlated with protection are a number of adipocyte-specific factors. These include the fat-cell-specific cytokines adipsin, resistin, and adiponectin and the adipocyte surface marker CD36. Interestingly, potentially protective T and B lymphocytes can be found embedded in the adipose tissue surrounding protected stomachs but never in control or unprotected stomachs. Adipsin-specific immunohistochemical staining of protected stomach sections further revealed molecular cross-talk between adjacent lymphoid and adipose cell populations. We propose a mechanism of protection that involves the effector responses of either or both lymphocyte subclasses as well as the previously unappreciated paracrine functions of adipose tissue surrounding the resident lymphocytes.