Direction 2. Cell-cell interactions between macrophages and other systems

The influence of macrophages on the development and homeostasis of various organs can be far-reaching.  Yet the normal roles and mechanisms of macrophages and microglia in the healthy body and brain, respectively, remain far less understood than their functions in disease and injury.  Of particular interest is the function of microglia in the healthy brain. Although not well understood, they have been implicated in shaping brain circuitry and neuronal development as well as in possibly affecting behavioral outcomes. We are addressing fundamental areas of macrophage biology in the context of how macrophages participate in the nervous system as well as other areas of the body prone to inflammation. We currently have interest in the following three areas. If you have interest in joining or collaborating with the Shiau Squad, please inquire with your particular area of interest to Celia at

Influence of microglia and innate immune system on brain circuitry and behavior

Impacts of peripheral inflammation outweigh that of microglia on routine daytime locomotor circuitry in larval zebrafish

Left, schematic of our long term daily routine locomotion tracking system using both 96- and 24- well chambers to test motility and exploratory behaviors respectively. Individual larvae at 5 dpf were distributed randomly one per well without their genotypes known until after completion of experimentation. Right, timecourse plots show significant drop in daytime swimming in a mutant that has systemic inflammation and lacks microglia. The locomotor deficit is reversed when macrophages are specifically restored in this mutant, providing evidence for the mutant macrophages as the cause for reduced daytime swimming. Read our work further: Kwon et al., 2022.

Outstanding questions we are seeking: how activated macrophages trigger neutrophil infiltration into the brain? how do activated neutrophils lingering in the brain affect the CNS or its locomotor output? which inflammatory pathways interfere with neural functions controlling daytime swimming? which CNS circuits with a focus on dopaminergic pathways are susceptible to effects of inflammation?

Indirect link between brain and liver mediated by macrophage infiltration

Localized brain microinjection leads to systemic circulation of stimuli activating macrophage infiltration into the liver in the early larval zebrafish prior to establishment of Kupffer cells.

Whole body imaging and tracing of injected substance from the brain revealed unusual and active infiltration of macrophages into the liver due to systemic circulation of LPS. Read our work further: Yang et al., 2020.

Outstanding questions we are seeking: how are resident Kupffer cells and infiltrating macrophages in the liver in common and different from one another? when and how do Kupffer cells establish? what roles do different types of macrophages play in the liver?

Role of intestinal macrophages in the enteric nervous system

Intestinal macrophages are tightly bundled with neural processes in the muscularis as well as in the mucosal region in the developing and adult zebrafish. We are investigating whether intestinal macrophages affect gut-brain communication.

Intestinal macrophages (green) are intimately connected and wrapping around enteric neural processes (blue). Read our work further: Graves et al., 2021.