Systemic inoculation of Escherichia coli causes emergency myelopoiesis in zebrafish larval caudal hematopoietic tissue

Abstract

Emergency granulopoiesis occurs in response to severe microbial infection. However, whether and how other blood components, particularly monocytes/macrophages and their progenitors, including hematopoietic stem/progenitor cells (HSPCs), participate in the process and the underlying molecular mechanisms remain unknown. In this study, we challenged zebrafish larvae via direct injection of Escherichia coli into the bloodstream, which resulted in systemic inoculation with this microbe. The reaction of hematopoietic cells, including HSPCs, in the caudal hematopoietic tissue was carefully analysed. Both macrophages and neutrophils clearly expanded following the challenge. Thus, emergency myelopoiesis, including monopoiesis and granulopoiesis, occurred following systemic bacterial infection. The HSPC reaction was dependent on the bacterial burden, manifesting as a slight increase under low burden, but an obvious reduction following the administration of an excessive volume of bacteria. Pu.1 was important for the effective elimination of the microbes to prevent excessive HSPC apoptosis in response to stress. Moreover, Pu.1 played different roles in steady and emergency monopoiesis. Although Pu.1 was essential for normal macrophage development, it played suppressive roles in emergency monopoiesis. Overall, our study established a systemic bacterial infection model that led to emergency myelopoiesis, thereby improving our understanding of the function of Pu.1 in this scenario.

Spatiotemporal Imaging and Pharmacokinetic of Fluorescent Compounds in Zebrafish Eleuthero-Embryos After Different Routes of Administration

“…The most commonly used injection site in zebrafish eleuthero-embryo is the yolk, consequently intra-yolk microinjections have also been automated [ 17,22 ]. Other routes to deliver compounds directly into larvae are intracardiac microinjections, as performed to evaluate the permeability of the blood-brain barrier by fluorescent compounds [ 23,24 ], and intravenous microinjection to evaluate systemic infection of bacterial strains in the zebrafish [ 25,26 ].…”

Zebrafish embryo sensitivity test as in vivo platform to anti-Shiga toxin compound screening

“…Zebrafish has already been used for the establishment of study models of bacteria infection and their consequences, such as the model of Salmonella infection [23]; Edwardsiella tarda [24], which is a model of pneumococcal meningitis [25]; Streptococcus agalactiae [26], an animal model for tuberculosis [27]; and Vibrio cholerae [28]. In E. coli, the majority of studies are focused on systemic infection and evaluation of inflammatory response using nonpathogenic strains [29][30][31].…”

IFN Signaling in Inflammation and Viral Infections: New Insights from Fish Models

“…In a recent work, Willis et al also demonstrated HSC-driven granulopoïesis in response to Shigella flexneri IC injection in zebrafish larvae [85]. Hematopoietic Stem and Progenitor Cell (HSPC) cell death in the context of uncontrolled bacterial burden, and a strong increase of inflammatory cytokine expression (TNFα, IFN 1–2, and IL1) has also been reported [86]. Altogether, these data have established that bacterial infections can increase hematopoiesis via cytokine signaling.…”