Wiegertjes Geert F, Wentzel Annelieke S, Spaink Herman P, Elks Philip M, Fink Inge R
Cell Biology and Immunology Group, Wageningen Institute of Animal Sciences, Wageningen University, P.O. Box 338, 6700 AH Wageningen, The Netherlands.
Cell Biology and Immunology Group, Wageningen Institute of Animal Sciences, Wageningen University, P.O. Box 338, 6700 AH Wageningen, The Netherlands.
Mol Immunol. 2016 Jan;69:146-56. doi: 10.1016/j.molimm.2015.09.026. Epub 2015 Oct 21.
In this review, we support taking polarized immune responses in teleost fish from a 'macrophage first' point of view, a hypothesis that reverts the dichotomous T helper (TH)1 and TH2 driving forces by building on the idea of conservation of innate immune responses in lower vertebrates. It is plausible that the initial trigger for macrophage polarization into M1 (inflammation) or M2 (healing) could rely only on sensing microbial/parasite infection or other innate danger signals, without the influence of adaptive immunity. Given the long and ongoing debate on the presence/absence of a typical TH1 cytokine environment and, in particular, TH2 cytokine environment in fish immune responses, it stands out that the presence of macrophages with polarized phenotypes, alike M1 and M2, have been relatively easy to demonstrate for fish. We summarize in short present knowledge in teleost fish on those cytokines considered most critical to the dichotomous development of TH1/M1 and TH2/M2 polarization, in particular, but not exclusively, interferon-γ and interleukin (IL)-4/IL-13. We review, in more detail, polarization of fish immune responses taken from the macrophage point of view for which we adopted the simple nomenclature of M1 and M2. We discuss inducible nitric oxide synthase, or NOS-2, as a reliable M1 marker and arginase-2 as a reliable M2 marker for teleost fish and discuss the value of these macrophage markers for the generation of zebrafish reporter lines to study M1/M2 polarization in vivo.
在本综述中，我们支持从“巨噬细胞优先”的角度看待硬骨鱼的极化免疫反应，这一假说通过基于低等脊椎动物固有免疫反应保守性的观点，颠覆了二分的辅助性T细胞（TH）1和TH2驱动力。巨噬细胞极化为M1（炎症）或M2（愈合）的初始触发因素仅依赖于感知微生物/寄生虫感染或其他固有危险信号，而不受适应性免疫的影响，这是合理的。鉴于关于鱼类免疫反应中典型TH1细胞因子环境尤其是TH2细胞因子环境是否存在的长期且仍在进行的争论，值得注意的是，对于鱼类而言，具有极化表型的巨噬细胞（如M1和M2）的存在相对容易证明。我们简要总结了目前硬骨鱼中关于那些对TH1/M1和TH2/M2极化二分发展最为关键的细胞因子的知识，特别是但不限于干扰素-γ和白细胞介素（IL）-4/IL-13。我们更详细地回顾了从巨噬细胞角度出发的鱼类免疫反应极化，为此我们采用了简单的M1和M2命名法。我们讨论了诱导型一氧化氮合酶（即NOS-2）作为硬骨鱼可靠的M1标志物以及精氨酸酶-2作为可靠的M2标志物，并讨论了这些巨噬细胞标志物对于生成斑马鱼报告系以在体内研究M1/M2极化的价值。
