Polarization of immune responses in fish: The 'macrophages first' point of view

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 (T-H)1 and T(H)2 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 T(H)1 cytokine environment and, in particular, T(H)2 cytokine environment in fish immune responses, it stands out that the presence of macrophages with polarized phenotypes, alike Ml 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 T(H)1/M1 and T(H)2/M2 polarization, in particular, but not exclusively, interferon-gamma 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. (C) 2015 Elsevier Ltd. All rights reserved.