Innate immune inflammatory response against enteric bacteria Helicobacter hepaticus induces mammary adenocarcinoma in mice
Innate immune inflammatory response against enteric bacteria Helicobacter hepaticus induces mammary adenocarcinoma in mice
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DOI：
10.1158/0008-5472.can-06-0558
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发表时间：
2006-08-01
期刊：
影响因子：
11.2
通讯作者：
Erdman, Susan E.
中科院分区：
文献类型：
--
作者：
Rao, Varada P.;Poutahidis, Theofilos;Erdman, Susan E.
与细菌感染相关的炎症是人类癌症的风险因素，但其在乳腺癌中的作用仍然知之甚少。我们先前已经表明，针对肠道细菌的先天免疫炎症反应足以诱导结肠癌。在这里，我们报告感染Rag 2缺陷C57 BL/6猿（Min/+）小鼠肠道细菌病原体，肝螺杆菌，显着促进乳腺癌的女性和增强肠腺瘤的多样性，肿瘤坏死因子α（TNF α）依赖性机制。通过过继转移具有白细胞介素10活性的CD 4（+）CD 45 RB（10）CD 25（+）调节（TR）细胞抑制乳腺和肠道肿瘤的发展以及促炎介质的增加。此外，供体小鼠预先暴露于H. hepaticus显著增强其T-R细胞的抗肿瘤效力。有趣的是，这些微生物经历的TR细胞在受体小鼠中更有效地抑制肿瘤发生，而不管它们的肿瘤病因。这些数据表明，肠道病原体的感染增强了T-R细胞的效力，并在以后的生活中预防上皮癌，这可能解释了在卫生习惯更严格的发达国家癌症风险的矛盾增加。人类肠道微生物感染失调可能导致解剖学上遥远的器官（如乳腺）发生癌症，这突出了在癌症预防和治疗中需要新的基于免疫的策略。
Inflammation associated with bacterial infections is a risk factor for cancers in humans, yet its role in breast cancer remains poorly understood. We have previously shown that innate immune inflammatory response against intestinal bacteria is sufficient to induce colon cancer. Here we report that infecting Rag2-deficient C57BL/6 Ape(Min/+) mice with an intestinal bacterial pathogen, Helicobacter hepaticus, significantly promotes mammary carcinoma in females and enhances intestinal adenoma multiplicity by a tumor necrosis factor alpha (TNF alpha)-dependent mechanism. The mammary and intestinal tumor development as well as the increase in proinflammatory mediators is suppressed by adoptive transfer of interleukin 10-competent CD4(+)CD45RB(10)CD25(+) regulatory (TR) cells. Furthermore, prior exposure of donor mice to H. hepaticus significantly enhances antitumor potency of their T-R cells. Interestingly, these microbially experienced TR cells suppress tumorigenesis more effectively in recipient mice irrespective of their tumor etiology. These data suggest that infections with enteric pathogens enhance T-R-Cell potency and protect against epithelial cancers later in life, potentially explaining paradoxical increases in cancer risk in developed countries having more stringent hygiene practices. The possibility that dysregulated gut microbial infections in humans may lead to cancer in anatomically distant organs, such as breast, highlights the need for novel immune-based strategies in cancer prevention and treatment.