肿瘤相关巨噬细胞极化的研究进展

肿瘤相关巨噬细胞是肿瘤组织局部浸润的巨噬细胞,在肿瘤组织微环境中,这些巨噬细胞发生M2型极化,从而发挥免疫抑制效应,促进肿瘤增殖。而M2型极化的肿瘤相关巨噬细胞也能够被再次诱导逆向极化形成具有抗肿瘤效应的M1型肿瘤相关巨噬细胞,激发机体产生特异性抗肿瘤免疫应答。促进肿瘤相关巨噬细胞M1型极化由此成为当前抗肿瘤免疫防治研究的热点。将对有关肿瘤相关巨噬细胞极化的新进展进行综述,为抗肿瘤免疫研究提供新的思路。     

巨噬细胞极化的研究进展

巨噬细胞是一群表型和功能均具有高度异质性的免疫细胞。巨噬细胞通过清除并修复受损的细胞和基质来维护组织完整性。巨噬细胞在不同的组织微环境、不同病理条件下,可极化成不同的表型即M1型巨噬细胞(经典活化的巨噬细胞)和M2型巨噬细胞(替代活化的巨噬细胞)。本文将对不同巨噬细胞亚群在抗细菌感染、抗寄生虫感染、哮喘、动脉粥样硬化和肿瘤产生中起到的的保护或致病作用,以及调控巨噬细胞极化的机制进行综述。掌握巨噬细胞极化在不同疾病中的作用以及调控巨噬细胞极化的具体机制,将为疾病的预防、诊断、治疗及药物研发提供新策略。     

凝血相关分子在病毒感染方面的研究进展

从生物进化角度,天然免疫系统、凝血系统、获得性免疫系统依次产生,且三者存在千丝万缕的联系.以病毒为研究对象对凝血系统作为免疫系统的一个独立部分进行研究,分两部分:感染初期,通过对凝血系统的调控来加强天然免疫和获得性免疫的对话,以此"通畅气血""增强免疫力",清除体内病毒;感染末期合并细菌感染,对凝血系统进行快速干预,既调动该系统自身的免疫力,也疏通天然免疫和获得性免疫的交流通道,有效逆转DIC状态挽救生命,为此,首先要了解各凝血相关分子在抗病毒感染中的作用.本综述分别介绍了多种病毒侵入后,所导致机体凝血功能紊乱的特点,以及在感染过程中凝血相关分子与免疫关联性特征,即病毒毒力分子如何通过调节凝血相关分子的表达,来影响免疫细胞的功能.同时,病毒毒力因子导致免疫系统的改变,又是如何间接影响凝血相关反应.将为包括新型冠状病毒在内的所有病毒的防控提供新的思路.     

巨噬细胞的极化及其意义

表型可变性和功能多样性是单个核吞噬细胞的重要特征。近年来巨噬细胞的极化受到关注。一般认为极化巨噬细胞是单核细胞活化后一系列功能状态两个极端。而它的分化受到各种微环境信号的诱导与调节。极化的巨噬细胞能够进一步影响局部免疫反应,与各种因子协同作用调节病原体微生物感染结局和肿瘤免疫,参与免疫调节,组织修复重塑过程。对巨噬细胞亚型诱导因素及功能的研究将有助于了解免疫反应的调节机制。     

PCL/β-TCP调控巨噬细胞极化对成血管效应的影响

目的:探究生物可降解材料聚己内酯/β-磷酸三钙(PCL/β-TCP)通过调控巨噬细胞极化对骨组织内血管生成的作用,为其临床应用提供依据。方法:采用3D打印技术制备试样并加以表征。体内实验采用模型为SD大鼠股骨远端植入模型。双侧植入PCL/β-TCP支架后采取免疫荧光染色观察支架内部成血管标记物CD31的表达差异,并采用血管灌注方法进行血管造影,评价支架内部血管体积。采用免疫荧光染色检测炎症标记物iNOS,抑炎标记物Arg-1的表达情况。体外实验采用细胞共培养的方式检测PCL/β-TCP对巨噬细胞极化的调控作用以及免疫介导的血管形成改变。实验分为两组,空白组(Control)及PCL/β-TCP(PT5)组。将巨噬细胞系Raw264.7接种于材料表面并对其极化水平及分泌改变进行检测。通过免疫荧光染色检测M1巨噬细胞标记物iNOS、M2巨噬细胞标记物Arg-1的表达情况。通过RT-qPCR检测CCR-7,CD206,血管内皮生长因子(VEGF),血小板源性生长因子(PDGF-BB),肿瘤坏死因子α(TNF-α),白细胞介素-10(IL-10)的转录情况。酶联免疫吸附试验(ELISA)检测VEGF、PDGF-BB、IL-10、TNF-α的分泌情况。应用Transwell迁移实验检测PCL/β-TCP刺激下巨噬细胞分泌作用对人脐静脉内皮细胞(HUVECs)迁移能力的影响,应用免疫荧光染色检测PCL/β-TCP刺激下巨噬细胞分泌作用对HUVECs表面血管形成指标CD31表达情况的影响。结果:在体内实验中,支架周围组织CD31表达升高(P0.001),血管灌注结果提示支架内部血管体积显著增加(P0.001),同时炎症标记物iNOS表达下调(P0.001),抗炎标记物Arg-1升高(P0.001)。在体外实验中,与Control相比,PT5组巨噬细胞中炎症标记物iNOS合成无明显差异,抑炎标记物Arg-1合成增加;炎症标记物CCR-7及TNF-α转录水平下调(P0.01,P0.01),抗炎标记物CD206及IL-10转录上调(P0.001,P0.001);VEGF转录水平下调(P0.01),PDGF-BB转录上调(P0.01);VEGF分泌水平下降(P0.001),PDGF-BB分泌增加(P0.01),IL-10分泌水平提高(P0.001),TNF-α分泌水平下降(P0.05)。在巨噬细胞分泌作用下,HUVECs的迁移能力提高(P0.001),CD31表达上调(P0.001)。结论:骨修复材料PCL/β-TCP可通过调控巨噬细胞向M2方向极化进而促进血管形成,可作为骨修复材料的候选材料之一。     

微RNA介导巨噬细胞极化的转录后调控

巨噬细胞极化是根据周围刺激环境做出表型调节的一个过程.一般极化为2个表型,分别为经典激活的M1巨噬细胞和替代激活的M2巨噬细胞.简而言之,M1巨噬细胞的特征是促炎和抗肿瘤;M2巨噬细胞是抗炎和促肿瘤.巨噬细胞极化被认为是人体生理和病理的关键调节器,其发挥作用的有效性依赖于关键因子的协调表达,而这些关键因子的表达在转录后...     

多糖调控巨噬细胞免疫应答机制的研究进展

多糖是一类来源广泛且具有多种生物学活性的天然大分子物质,能增强机体先天性和适应性免疫系统。近来研究发现,生物活性多糖能通过巨噬细胞表面多种受体诱导复杂而又交叉的信号转导,调控细胞功能和相关细胞因子的表达,但对于相关的研究缺乏系统的归纳分析。该文综述了生物多糖对巨噬细胞的免疫调节作用、刺激信号通路以及多糖结构与受体关系,旨在为相关领域的研究提供参考。     

病毒感染中细胞自噬研究进展

细胞自噬是一种依赖于溶酶体的细胞内降解途径,用于细胞维持内环境的稳态.自噬广泛存在于真核细胞的生理、病理过程中.研究发现自噬与病毒之间的相互作用是一个复杂且多向化的过程,一方面自噬能够参与机体免疫应答、发挥抗病毒效应;另一方面,细胞的自噬机制也可被病毒操纵,以利于其自身复制.本文对近年来细胞自噬与病毒感染的相互作用进展,尤其是病毒如何调控自噬以促进其复制和致病的机制加以综述.     

肠道病毒调控固有免疫的分子机制研究进展

肠道病毒属于小核糖核酸病毒科,包括脊髓灰质炎病毒等多种重要人类病原体,已成为全球公共卫生安全的重大威胁之一。固有免疫是机体早期抵御病毒感染的重要防线。不同肠道病毒在进化中已经具备了多种途径躲避免疫识别或诱导固有免疫系统失活。本文重点对肠道病毒调控宿主固有免疫的相关分子机制进行综述,系统整理了肠道病毒逃避干扰素依赖与干扰素非依赖的抗病毒固有免疫防御的分子特征与作用规律,为肠道病毒致病机制的探究和抗病毒药物的研发提供参考。     

姜黄素激活PPAR-γ通路改变巨噬细胞的极化状态

过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptorγ,PPAR-γ)通路是调节替换活化的(alternatively activated)M2型巨噬细胞极化的中心环节.姜黄素是PPAR-γ的天然激动剂,有着良好的抗炎作用.本研究通过建立巨噬细胞株的体外炎症模型,用姜黄素及PPAR-γ的特异性抑制剂GW9662对其进行干预,观察巨噬细胞株极化状态的改变.结果显示,姜黄素可以促使巨噬细胞向M2型极化,当特异性抑制PPAR-γ通路后,姜黄素促进巨噬细胞向M2型极化的作用受到抑制.结果表明,姜黄素可能是通过激动PPAR-γ通路促使巨噬细胞向M2型极化,为进一步研究姜黄素的抗炎机制及治疗慢性低度炎症相关的代谢性疾病提供了一个新的思路.     

Integration of Toll-like receptor and phagocytic signaling for tailored immunity

Toll-like receptors (TLRs) are recruited to phagosomes and sample the contents of the compartment for microbial products. In this review, we discuss the relationship between phagocytosis and TLRs from two additional perspectives: first, TLR signaling modulates phagocytosis; second, phagocytosis modulates the consequences of TLR activation.     

Integrin activation and viral infection

Integrins are members of a ubiquitous membrane receptor family which includes 18 different α subunits and 8 β subunits forming more than 20 α/β heterodimers. Integrins play key functions in vascular endothelial cell and tumour cell adhesion, lymphocyte trafficking, tumor growth and viral infection. Current understanding of the molecular basis of integrins as viral receptors has been achieved through many decades of study into the biology of transmembrane glycoproteins and their interactions with several viruses. This review provides a summary of the current knowledge on the molecular bases of interactions between viruses and integrins, which are of potential practical significance. Inhibition of virus-integrin interactions at the points of virus attachment or entry will provide a novel approach for the therapeutic treatment of viral diseases. Foundation item: The National key Basic Research (973) Program (2005CB523201) and National Key Technology R&D Program (2006BAD06A14)     

Advances in Nod-like receptors (NLR) biology

The innate immune system is composed of a wide repertoire of conserved pattern recognition receptors (PRRs) able to trigger inflammation and host defense mechanisms in response to endogenous or exogenous pathogenic insults. Among these, nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) are intracellular sentinels of cytosolic sanctity capable of orchestrating innate immunity and inflammatory responses following the perception of noxious signals within the cell. In this review, we elaborate on recent advances in the signaling mechanisms of NLRs, operating within inflammasomes or through alternative inflammatory pathways, and discuss the spectrum of their effector functions in innate immunity. We describe the progressive characterization of each NLR with associated controversies and cutting edge discoveries.     

Homology, disruption and phenotypic analysis of CaGS Candida albicans gene induced during macrophage infection

During macrophage infection Candida albicans expresses differentially several genes whose functions are associated with its survival strategy. Among others, we have isolated CaGS gene, which is homologous to SNF3, a glucose sensor of Saccharomyces cerevisiae. To elucidate its potential role during infection, CaGS has been disrupted and the resulting phenotype analyzed on different solid media. The null mutant lost the ability to form hyphae on a medium with low glucose concentration and serum. Furthermore, this mutant does not disrupt macrophage in in vitro infections. We believe that this putative glucose sensor is involved in hyphal development during macrophage infection.     

Opposing roles of IL-10 in acute bacterial infection

Interleukin-10 (IL-10) is recognized as an anti-inflammatory cytokine that downmodulates inflammatory immune responses at multiple levels. In innate cells, production of this cytokine is usually triggered after pathogen recognition receptor (PRR) engagement by pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patters (DAMPs), as well as by other soluble factors. Importantly, IL-10 is frequently secreted during acute bacterial infections and has been described to play a key role in infection resolution, although its effects can significantly vary depending on the infecting bacterium. While the production of IL-10 might favor host survival in some cases, it may also result harmful for the host in other circumstances, as it can prevent appropriate bacterial clearance. In this review we discuss the role of IL-10 in bacterial clearance and propose that this cytokine is required to recover from infection caused by extracellular or highly pro-inflammatory bacteria. Altogether, we propose that IL-10 drives excessive suppression of the immune response upon infection with intracellular bacteria or in non-inflammatory bacterial infections, which ultimately favors bacterial persistence and dissemination within the host. Thus, the nature of the bacterium causing infection is an important factor that needs to be taken into account when considering new immunotherapies that consist on the modulation of inflammation, such as IL-10. Indeed, induction of this cytokine may significantly improve the host’s immune response to certain bacteria when antibiotics are not completely effective.     

Unfolding the relationship between secreted molecular chaperones and macrophage activation states

Over the last 20 years, it has emerged that many molecular chaperones and protein-folding catalysts are secreted from cells and function, somewhat in the manner of cytokines, as pleiotropic signals for a variety of cells, with much attention being focused on the macrophage. During the last decade, it has become clear that macrophages respond to bacterial, protozoal, parasitic and host signals to generate phenotypically distinct states of activation. These activation states have been termed ‘classical’ and ‘alternative’ and represent not a simple bifurcation in response to external signals but a range of cellular phenotypes. From an examination of the literature, the hypothesis is propounded that mammalian molecular chaperones are able to induce a wide variety of alternative macrophage activation states, and this may be a system for relating cellular or tissue stress to appropriate macrophage responses to restore homeostatic equilibrium.     

Regulation of RIG-I-like receptor signaling by host and viral proteins

Vertebrate innate immunity is characterized by an effective immune surveillance apparatus, evolved to sense foreign structures, such as proteins or nucleic acids of invading microbes. RIG-I-like receptors (RLRs) are key sensors of viral RNA species in the host cell cytoplasm. Activation of RLRs in response to viral RNA triggers an antiviral defense program through the production of hundreds of antiviral effector proteins including cytokines, chemokines, and host restriction factors that directly interfere with distinct steps in the virus life cycle. To avoid premature or abnormal antiviral and proinflammatory responses, which could have harmful consequences for the host, the signaling activities of RLRs and their common adaptor molecule, MAVS, are delicately controlled by cell-intrinsic regulatory mechanisms. Furthermore, viruses have evolved multiple strategies to modulate RLR-MAVS signal transduction to escape from immune surveillance. Here, we summarize recent progress in our understanding of the regulation of RLR signaling through host factors and viral antagonistic proteins.