Host-microbe interactions in the developing zebrafish

Abstract

The amenability of the zebrafish to in vivo imaging and genetic analysis has fueled expanded use of this vertebrate model to investigate the molecular and cellular foundations of host-microbe relationships. Study of microbial encounters in zebrafish hosts has concentrated on developing embryonic and larval stages, when the advantages of the zebrafish model are maximized. A comprehensive understanding of these host-microbe interactions requires appreciation of the developmental context into which a microbe is introduced, as well as the effects of that microbial challenge on host ontogeny. In this review, we discuss how in vivo imaging and genetic analysis in zebrafish has advanced our knowledge of host-microbe interactions in the context of a developing vertebrate host. We focus on recent insights into immune cell ontogeny and function, commensal microbial relationships in the intestine, and microbial pathogenesis in zebrafish hosts.

Figure 1. Developmental milestones in zebrafish host-microbe interactions

Schematic depiction of anatomical sites (A) and approximate durations (B) of hematopoietic activity in developing zebrafish. The eye (e), yolk (y) and gastrointestinal tract (gray) are indicated in A. Relocation of definitive hematopoietic stem cells (HSCs) between sites is represented by arrows in B. Primitive erythropoiesis occurs in the intermediate cell mass (ICM, blue) which is active ∼11-30hpf [59], whereas primitive myelopoiesis begins in the rostral blood island (RBI) and later the yolk (pink) from ∼12-40hpf [11]. HSCs appear in the aorta-gonad-mesonephros region (AGM, red) ∼26hpf until ∼3dpf [15,16]. These HSCs are mobilized to seed the caudal hematopoietic tissue (PBI/CHT; green) and pronephros (brown) as early as 32hpf, and the thymus (purple) as early as 48hpf [14-17]. Definitive hematopoiesis in the CHT begins de novo ∼24hpf [13] and continues until at least 14dpf [14]. Cells from the CHT contribute to the pronephros and thymus as early as 48hpf [14,15]. B cell development initiates in the pancreas (orange) starting 4dpf [21], although the hematopoietic origins of these cells remain unknown. The thymus, pancreas, and pronephros/kidney subsequently serve as sites of definitive hematopoiesis into adult stages [9,10]. (C) Within this dynamic developmental context, important milestones relevant to zebrafish immunity and microbial interactions are indicated and referenced.