Abstract：
BACKGROUND: An event of increasing interest during host-pathogen interactions is the polarization of patrolling/naive monocytes (MOs) into macrophage subsets (MФs). Therapeutic strategies aimed at modulating this event are under investigation.
METHODS: This review focuses on the mechanisms of induction/development and profile of MФs polarized toward classically proinflammatory (M1) or alternatively anti-inflammatory (M2) phenotypes in response to bacteria, fungi, parasites, and viruses.
CONCLUSIONS: It highlights nuclear, cytoplasmic, and cell surface receptors (pattern recognition receptors/PPRs), microenvironmental mediators, and immune signaling. MФs polarize into phenotypes: M1 MФs, activated by IFN-γ, pathogen-associated molecular patterns (PAMPs, e.g. lipopolysaccharide) and membrane-bound PPRs ligands (TLRs/CLRs ligands); or M2 MФs, induced by interleukins (ILs-4, -10 and -13), antigen-antibody complexes, and helminth PAMPs. Polarization toward M1 and M2 profiles evolve in a pathogen-specific manner, with or without canonicity, and can vary widely. Ultimately, this can result in varying degrees of host protection or more severe disease outcome. On the one hand, the host is driving effective MФs polarization (M1 or M2); but on the other hand, microorganisms may skew the polarization through virulence factors to increase pathogenicity. Cellular/genomic reprogramming also ensures plasticity of M1/M2 phenotypes. Because modulation of polarization can occur at multiple points, new insights and emerging perspectives may have clinical implications during the inflammation-to-resolution transition; translated into practical applications as for therapeutic/vaccine design target to boost microbicidal response (M1, e.g. triggering oxidative burst) with specifics PAMPs/IFN-γ or promote tissue repair (M2, increasing arginase activity) via immunotherapy.
Monocytes are white blood cells (leukocytes) that help fight off various types of aggressive agents, including microorganisms (bacteria, fungi, viruses, and parasites), and help maintain the healthy balance of the human body. These cells differentiate into specific macrophages in tissues such as the lungs, heart, liver, skin, and brain. The present review focuses on the peculiar cellular properties that macrophages can acquire during the human immune response to infectious diseases. In this regard, it is discussed that macrophages are didactically divided into M1 and M2 subtypes. The first subtype (M1) is responsible for fighting pathogens and causing inflammation. The second subtype (M2) is mainly responsible for healing and repairing damaged tissue. Current knowledge shows that although both subtypes are involved in the same immune response aimed at protecting the human body, these M1 and M2 profiles have different characteristics that have implications for therapeutic measures such as developing specific drugs or vaccines to balance the immune response against a given pathogen and promote a complete cure of the disease. Alongside the therapeutic impacts, this review also looks at the characteristics that allow aggressive microorganisms to counteract the immune response developed by these M1 and M2 cell profiles. It highlights how exactly there can be greater protection or detriment to the human host against a given microorganism when there is a predilection to develop a more abundant immune response from one of the two profiles (M1 or M2).
METHODS: This review focuses on the mechanisms of induction/development and profile of MФs polarized toward classically proinflammatory (M1) or alternatively anti-inflammatory (M2) phenotypes in response to bacteria, fungi, parasites, and viruses.
CONCLUSIONS: It highlights nuclear, cytoplasmic, and cell surface receptors (pattern recognition receptors/PPRs), microenvironmental mediators, and immune signaling. MФs polarize into phenotypes: M1 MФs, activated by IFN-γ, pathogen-associated molecular patterns (PAMPs, e.g. lipopolysaccharide) and membrane-bound PPRs ligands (TLRs/CLRs ligands); or M2 MФs, induced by interleukins (ILs-4, -10 and -13), antigen-antibody complexes, and helminth PAMPs. Polarization toward M1 and M2 profiles evolve in a pathogen-specific manner, with or without canonicity, and can vary widely. Ultimately, this can result in varying degrees of host protection or more severe disease outcome. On the one hand, the host is driving effective MФs polarization (M1 or M2); but on the other hand, microorganisms may skew the polarization through virulence factors to increase pathogenicity. Cellular/genomic reprogramming also ensures plasticity of M1/M2 phenotypes. Because modulation of polarization can occur at multiple points, new insights and emerging perspectives may have clinical implications during the inflammation-to-resolution transition; translated into practical applications as for therapeutic/vaccine design target to boost microbicidal response (M1, e.g. triggering oxidative burst) with specifics PAMPs/IFN-γ or promote tissue repair (M2, increasing arginase activity) via immunotherapy.
Monocytes are white blood cells (leukocytes) that help fight off various types of aggressive agents, including microorganisms (bacteria, fungi, viruses, and parasites), and help maintain the healthy balance of the human body. These cells differentiate into specific macrophages in tissues such as the lungs, heart, liver, skin, and brain. The present review focuses on the peculiar cellular properties that macrophages can acquire during the human immune response to infectious diseases. In this regard, it is discussed that macrophages are didactically divided into M1 and M2 subtypes. The first subtype (M1) is responsible for fighting pathogens and causing inflammation. The second subtype (M2) is mainly responsible for healing and repairing damaged tissue. Current knowledge shows that although both subtypes are involved in the same immune response aimed at protecting the human body, these M1 and M2 profiles have different characteristics that have implications for therapeutic measures such as developing specific drugs or vaccines to balance the immune response against a given pathogen and promote a complete cure of the disease. Alongside the therapeutic impacts, this review also looks at the characteristics that allow aggressive microorganisms to counteract the immune response developed by these M1 and M2 cell profiles. It highlights how exactly there can be greater protection or detriment to the human host against a given microorganism when there is a predilection to develop a more abundant immune response from one of the two profiles (M1 or M2).
摘要：
背景：在宿主-病原体相互作用过程中引起兴趣的事件是巡逻/幼稚单核细胞（MO）极化为巨噬细胞亚群（MΦs）。旨在调节该事件的治疗策略正在研究中。
方法：这篇综述集中于对细菌的反应中，向经典的促炎（M1）或抗炎（M2）表型极化的诱导/发展和分布的机制，真菌,寄生虫,和病毒。
结论：它突出了核，细胞质，和细胞表面受体（模式识别受体/PPRs），微环境介体，和免疫信号。MΦs极化为表型：M1MΦs，由IFN-γ激活，病原体相关分子模式(PAMPs，例如脂多糖)和膜结合PPRs配体(TLRs/CLRs配体)；或M2MΦs，由白细胞介素（IL-4，-10和-13）诱导，抗原-抗体复合物，和蠕虫PAMP。向M1和M2谱的极化以病原体特异性方式进化，不管有没有规范，并且可以变化很大。最终,这可能导致不同程度的宿主保护或更严重的疾病后果。一方面,主机正在驱动有效的MΦs极化(M1或M2)；但另一方面，微生物可能通过毒力因子扭曲极化以增加致病性。细胞/基因组重编程还确保M1/M2表型的可塑性。因为偏振的调制可以发生在多个点,新的见解和新出现的观点可能在炎症到消退的转变过程中具有临床意义;转化为治疗/疫苗设计目标的实际应用,以通过特异性PAMPs/IFN-γ增强杀微生物反应(M1,例如触发氧化爆发)或通过免疫治疗促进组织修复(M2,增加精氨酸酶活性).
单核细胞是白血细胞（白细胞），有助于击退各种类型的攻击因子，包括微生物（细菌，真菌,病毒,和寄生虫)，并帮助维持人体的健康平衡。这些细胞在肺等组织中分化为特定的巨噬细胞，心,肝脏,皮肤,和大脑。本综述的重点是巨噬细胞在人类对传染病的免疫反应过程中可以获得的特殊细胞特性。在这方面,讨论了巨噬细胞在教学上分为M1和M2亚型。第一亚型(M1)负责对抗病原体并引起炎症。第二亚型(M2)主要负责愈合和修复受损组织。目前的知识表明，尽管两种亚型都参与了旨在保护人体的相同免疫反应，这些M1和M2谱具有不同的特征,这些特征对治疗措施有影响,例如开发特定药物或疫苗以平衡针对给定病原体的免疫应答并促进疾病的完全治愈.除了治疗影响，这篇综述还研究了允许侵袭性微生物抵消由这些M1和M2细胞谱产生的免疫应答的特征.它突出了当存在从两个谱(M1或M2)中的一个产生更丰富的免疫应答的倾向时,人类宿主对给定微生物的确切保护或损害如何。
方法：这篇综述集中于对细菌的反应中，向经典的促炎（M1）或抗炎（M2）表型极化的诱导/发展和分布的机制，真菌,寄生虫,和病毒。
结论：它突出了核，细胞质，和细胞表面受体（模式识别受体/PPRs），微环境介体，和免疫信号。MΦs极化为表型：M1MΦs，由IFN-γ激活，病原体相关分子模式(PAMPs，例如脂多糖)和膜结合PPRs配体(TLRs/CLRs配体)；或M2MΦs，由白细胞介素（IL-4，-10和-13）诱导，抗原-抗体复合物，和蠕虫PAMP。向M1和M2谱的极化以病原体特异性方式进化，不管有没有规范，并且可以变化很大。最终,这可能导致不同程度的宿主保护或更严重的疾病后果。一方面,主机正在驱动有效的MΦs极化(M1或M2)；但另一方面，微生物可能通过毒力因子扭曲极化以增加致病性。细胞/基因组重编程还确保M1/M2表型的可塑性。因为偏振的调制可以发生在多个点,新的见解和新出现的观点可能在炎症到消退的转变过程中具有临床意义;转化为治疗/疫苗设计目标的实际应用,以通过特异性PAMPs/IFN-γ增强杀微生物反应(M1,例如触发氧化爆发)或通过免疫治疗促进组织修复(M2,增加精氨酸酶活性).
单核细胞是白血细胞（白细胞），有助于击退各种类型的攻击因子，包括微生物（细菌，真菌,病毒,和寄生虫)，并帮助维持人体的健康平衡。这些细胞在肺等组织中分化为特定的巨噬细胞，心,肝脏,皮肤,和大脑。本综述的重点是巨噬细胞在人类对传染病的免疫反应过程中可以获得的特殊细胞特性。在这方面,讨论了巨噬细胞在教学上分为M1和M2亚型。第一亚型(M1)负责对抗病原体并引起炎症。第二亚型(M2)主要负责愈合和修复受损组织。目前的知识表明，尽管两种亚型都参与了旨在保护人体的相同免疫反应，这些M1和M2谱具有不同的特征,这些特征对治疗措施有影响,例如开发特定药物或疫苗以平衡针对给定病原体的免疫应答并促进疾病的完全治愈.除了治疗影响，这篇综述还研究了允许侵袭性微生物抵消由这些M1和M2细胞谱产生的免疫应答的特征.它突出了当存在从两个谱(M1或M2)中的一个产生更丰富的免疫应答的倾向时,人类宿主对给定微生物的确切保护或损害如何。
