Mobilisation and dysfunction of haematopoietic stem/progenitor cells after Listonella anguillarum infection in ayu, Plecoglossus altivelis

Xin-Jiang Lu,Jiong Chen,Qiang Chen,Ye-Jing Rong

doi:10.1038/srep28082

Abstract

Haematopoietic stem/progenitor cells (HSPCs) can mobilise into blood and produce immune cell lineages following stress. However, the homeostasis and function of HSPCs after infection in teleosts are less well known. Here, we report that Listonella anguillarum infection enhances HSPC mobilisation and reduces their differentiation into myeloid cells in ayu (Plecoglossus altivelis), an aquacultured teleost in East Asia. We established a colony-forming unit culture (CFU-C) assay to measure HSPCs using conditioned medium from peripheral blood mononuclear cells stimulated with phytohaemagglutinin. The number of CFU-Cs decreased in the head kidney and increased in the blood and spleen of ayu infected with L. anguillarum. HSPC mobilisation after L. anguillarum infection was mediated by norepinephrine. Furthermore, HSPCs from ayu treated with L. anguillarum lipopolysaccharide (LPS) showed defective myeloid differentiation and could no longer rescue L. anguillarum-infected ayu. HSPC expansion was suppressed after L. anguillarum infection or its LPS treatment in vitro. These results reveal a link between HSPC regulation and pathogen infection in teleosts.

Highlights

Haematopoietic stem/progenitor cells (HSPCs) can mobilise into blood and produce immune cell lineages following stress
On the basis of previous flow cytometry-based separation of major blood cell lineages from the zebrafish kidney[14], the separations in this study were as follows: myelomonocytic cells, mainly including neutrophils, monocytes, and macrophages, were in an FSChiSSChi population (R1); lymphoid cells were enriched in an FSCloSSClo subset (R2); and HSPC-enriched cells were in an FSChiSSCint subset (R3, Fig. 1B)
We found that the PHA CM stimulated the formation of colony-forming unit-culture (CFU-C), which represents HSPC activity

Summary

Introduction

Haematopoietic stem/progenitor cells (HSPCs) can mobilise into blood and produce immune cell lineages following stress. Several studies have reported the mechanisms underlying HSPC homeostasis, self-renewal, and differentiation in mammals, the process and mechanism of HSPC mobilisation and function in teleosts are less well known. In response to a systemic infection, such as with Escherichia coli, HSPCs expand, mobilise, and differentiate[7] Some pathogens, such as Ehrlichia chaffeensis or Anaplasma phagocytophilum, reduce HSPC numbers and the cellularity of bone marrow[8,9]. Owing to their small body size, in vivo functional analysis of haematopoietic cells in zebrafish is difficult Teleosts possess both adaptive and innate immune systems, which are similar to, and in some cases different from, mammalian immune system[20]. More investigation is needed to elucidate HSPC homeostasis in teleosts after infection with its pathogens

Methods

Results

Conclusion