Macrophage–Microbe Interactions: Lessons from the Zebrafish Model

Abstract

Macrophages provide front line defense against infections. The study of macrophage–microbe interplay is thus crucial for understanding pathogenesis and infection control. Zebrafish (Danio rerio) larvae provide a unique platform to study macrophage–microbe interactions in vivo, from the level of the single cell to the whole organism. Studies using zebrafish allow non-invasive, real-time visualization of macrophage recruitment and phagocytosis. Furthermore, the chemical and genetic tractability of zebrafish has been central to decipher the complex role of macrophages during infection. Here, we discuss the latest developments using zebrafish models of bacterial and fungal infection. We also review novel aspects of macrophage biology revealed by zebrafish, which can potentiate development of new therapeutic strategies for humans.

Macrophages target Salmonella by Lc3-associated phagocytosis in a systemic infection model

“…We have previously shown that zebrafish embryos respond to Salmonella infection by Toll-like receptor-mediated signaling inducing a strong proinflammatory gene expression signature similar as in mammalian hosts and human cells [38][39][40][41]. The zebrafish has become a widely utilized vertebrate model for human infection diseases, especially because microscopic imaging of infected zebrafish embryos provides new possibilities to gain insight into the interactions between pathogens and host innate immune cells in a living organism [42][43][44]. The zebrafish is also increasingly used to study autophagy and it has previously been demonstrated that zebrafish embryos can mount an autophagic defense response against Shigella flexneri and Mycobacterium marinum [45][46][47][48].…”

Determining macrophage versus neutrophil contributions to innate immunity using larval zebrafish

“…Excellent recent zebrafish innate immunity reviews have focused on findings related to the specific functions of macrophages (Yoshida et al, 2017;Torraca et al, 2014) or neutrophils (Henry et al, 2013;Harvie and Huttenlocher, 2015), or immunity in specific contexts such as infection (Gomes and Mostowy, 2019;Rosowski et al, 2018b;Masud et al, 2017). The purpose of this Review is to provide a broader view of the role of these cell types in diverse biological situations, and to compare and contrast different depletion methods to perhaps explain disparate results and interpretations in the literature.…”

In vivocontrol ofToxoplasma gondiiby zebrafish macrophages

“…GRA2 staining and CLEM of replicating tachyzoites strongly suggests PV formation and is indicative of normal type I parasite behavior as demonstrated in vitro using tissue culture cells and in vivo using other animal models (39). The zebrafish HBV is well established to investigate host response to infection (30)(31)(32). We do not observe Toxoplasma dissemination from the HBV and this allows us to monitor leukocyte-parasite interactions in a localized area.…”

“…Therefore, to complement in vivo murine studies, a novel animal model can benefit analysis of Toxoplasma control on a cellular and molecular level. Zebrafish are a well-established model for studying infection and immunity (29)(30)(31)(32). Coupled with their optical accessibility during early development, zebrafish larvae are highly suited for non-invasive study of Toxoplasma infection and host response in real-time in vivo (31,32).…”