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作为肿瘤微生物生态失调传感器的Toll样受体:对癌症进展的影响

Toll Like Receptors as Sensors of the Tumor Microbial Dysbiosis: Implications in Cancer Progression.

作者信息

Le Noci Valentino, Bernardo Giancarla, Bianchi Francesca, Tagliabue Elda, Sommariva Michele, Sfondrini Lucia

机构信息

Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy.

U.O. Laboratorio di Morfologia Umana Applicata, IRCCS Policlinico San Donato, Milan, Italy.

出版信息

Front Cell Dev Biol. 2021 Sep 17;9:732192. doi: 10.3389/fcell.2021.732192. eCollection 2021.

Abstract

The microbiota is a complex ecosystem of active microorganisms resident in the body of mammals. Although the majority of these microorganisms resides in the distal gastrointestinal tract, high-throughput DNA sequencing technology has made possible to understand that several other tissues of the human body host their own microbiota, even those once considered sterile, such as lung tissue. These bacterial communities have important functions in maintaining a healthy body state, preserving symbiosis with the host immune system, which generates protective responses against pathogens and regulatory pathways that sustain the tolerance to commensal microbes. Toll-like receptors (TLRs) are critical in sensing the microbiota, maintaining the tolerance or triggering an immune response through the direct recognition of ligands derived from commensal microbiota or pathogenic microbes. Lately, it has been highlighted that the resident microbiota influences the initiation and development of cancer and its response to therapies and that specific changes in the number and distribution of taxa correlate with the existence of cancers in various tissues. However, the knowledge of functional activity and the meaning of microbiome changes remain limited. This review summarizes the current findings on the function of TLRs as sensors of the microbiota and highlighted their modulation as a reflection of tumor-associated changes in commensal microbiota. The data available to date suggest that commensal "onco-microbes" might be able to break the tolerance of TLRs and become complicit in cancer by sustaining its growth.

摘要

微生物群是哺乳动物体内活跃微生物组成的复杂生态系统。尽管这些微生物大多存在于胃肠道远端,但高通量DNA测序技术使人们有可能了解到人体的其他几个组织也有自身的微生物群,甚至包括那些曾被认为无菌的组织,如肺组织。这些细菌群落对于维持健康的身体状态、与宿主免疫系统保持共生关系具有重要作用,宿主免疫系统会产生针对病原体的保护性反应以及维持对共生微生物耐受性的调节途径。Toll样受体(TLRs)在感知微生物群、通过直接识别共生微生物群或致病微生物衍生的配体来维持耐受性或触发免疫反应方面至关重要。最近,有研究强调常驻微生物群会影响癌症的发生和发展及其对治疗的反应,而且微生物分类群数量和分布的特定变化与各种组织中癌症的存在相关。然而,关于微生物群功能活性及其变化意义的了解仍然有限。本综述总结了目前关于TLRs作为微生物群传感器功能的研究结果,并强调了它们的调节作用,以此反映共生微生物群中与肿瘤相关的变化。目前可得的数据表明,共生“致癌微生物”可能会打破TLRs的耐受性,并通过促进肿瘤生长而参与癌症发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b59b/8485072/08583f5c6bd6/fcell-09-732192-g001.jpg

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