Xenopus: An in vivo model for imaging the inflammatory response following injury and bacterial infection

Abstract

A major goal in regenerative medicine is to identify therapies to facilitate our body׳s innate abilities to repair and regenerate following injury, disease or aging. In the past decade it has become apparent that the innate immune system is able to affect the speed and quality of the regenerative response through mechanisms that are not entirely clear. For this reason there has been a resurgent interest in investigating the role of inflammation during tissue repair and regeneration. Remarkably, there have only been a handful of such studies using organisms with high regenerative capacity. Here we perform a study of the inflammatory response following injury in Xenopus larvae, which are able to achieve scarless wound healing and to regenerate appendages, as a preamble into understanding the role that inflammation plays during tissue repair and regeneration in this organism. We characterized the morphology and migratory behavior of granulocytes and macrophages following sterile and infected wounding regimes, using various transgenic lines that labeled different types of myeloid lineages, including granulocytes and macrophages. Using this approach we found that the inflammatory response following injury and infection in Xenopus larvae is very similar to that seen in humans, suggesting that this model provides an easily tractable and medically relevant system to investigate inflammation following injury and infection in vivo.

Learning from regeneration research organisms: The circuitous road to scar free wound healing

“…Several studies in Xenopus spp. now confirm a connection between the development of the immune system and the loss of regenerative ability (King et al, 2012; Mescher et al, 2013; Mescher et al, 2017; Paredes et al, 2015). …”

Evolutionary Aspects of Macrophages Polarization

“…As in zebrafish, several transgenic lines with different subsets of myeloid lineages labeled with different colored fluorescent proteins have been characterized (Paredes et al 2015). These lines include: a xLurp1 :EGFP Tg line in which myeloid cells (e.g., granulocytes and monocytic leukocytes) express EGFP under the xLurp (Ly-6/uPAR-related protein) promoter (Paredes et al 2015; Smith et al 2002); a xmpeg :mCherry Tg line in which only mononuclear phagocytes (i.e., mainly macrophages) express the red fluorescence label mCherry under the zebrafish macrophage-specific mpeg promoter (Ellett et al 2011); and a double mpeg1 : mCherry and x lurp1 :GFP line (Paredes et al 2015).…”

Using Xenopus to understand human disease and developmental disorders

“…While it has been an outstanding system in which to make fundamental discoveries, Xenopus has also played a major role in understanding pathological processes. For example, Xenopus has been used to advance our understanding of DNA damage response and apoptosis (Kermi et al, ; McCoy et al, ; Olivera Harris et al, ; Shi et al, ; Tammaro, Liao, Beeharry, & Yan, ), immune and inflammatory responses (Edholm, Grayfer, De Jesús Andino, & Robert, ; Grayfer & Robert, 2014; Haynes‐Gilmore et al, ; Paredes, Ishibashi, Borrill, Robert, & Amaya, ; Wangkanont, Wesener, Vidani, Kiessling, & Forest, ), regenerative plasticity and wound healing (Franchini & Bertolotti, ; Hayashi et al, ; Muñoz et al, ; Wang & Beck, ; Wang, Keenan, Lynn, McEwan, & Beck, ), and responses to environmental toxicity (Chen, Wang, Zhu, Ding, & Peng, ; Hellyer et al, ; Sai et al, ). In addition, it has been used to great advantage in the development of therapeutics (e.g., Quadri, Papke, & Horenstein, ; Rodrigues et al, ; Volkman et al, 2016).…”