The central nervous system (CNS) harbors various myeloid compartments, including parenchyma microglia, perivascular macrophages, dendritic cells, and granulocytes. These myeloid lineages, together, establish an immune network to play different functions in both homeostasis and inflammatory conditions. Although myeloid cell compartmentalization has been reported in murine and human, little is known about the myeloid heterogeneity in the CNS of lower vertebrates. Here, we have determined two phenotypically and functionally distinct myeloid populations in the brain of adult zebrafish. The conventional microglia, marked by ccl34b.1, are highly mobile and present active phagocytotic activity. On the other hand, the Brain-associated DCs, which do not express ccl34b.], are more ramified in sha...[ Read more ]

The central nervous system (CNS) harbors various myeloid compartments, including parenchyma microglia, perivascular macrophages, dendritic cells, and granulocytes. These myeloid lineages, together, establish an immune network to play different functions in both homeostasis and inflammatory conditions. Although myeloid cell compartmentalization has been reported in murine and human, little is known about the myeloid heterogeneity in the CNS of lower vertebrates. Here, we have determined two phenotypically and functionally distinct myeloid populations in the brain of adult zebrafish. The conventional microglia, marked by ccl34b.1, are highly mobile and present active phagocytotic activity. On the other hand, the Brain-associated DCs, which do not express ccl34b.], are more ramified in shape and have limited phagocytosis ability. The functions of the two myeloid populations are further elucidated under homeostatic and bacterial infection conditions, in which microglia actively involve in bacterial clearance and Brain-associated DCs secrete regulatory molecules. Moreover, the genetic network governing the development of the two CNS myeloid populations is also investigated. We show that the inhibitor of DNA binding 2a (id2a) and the basic leucine zipper ATF-like transcription factor 3 (batf3) are required for the early development of ramified Brain-associated DCs, and batf3 acts downstream of id2a during this process. In contrast, the zinc finger E-box-binding homeobox 2a (zeb2a) promotes the formation of microglia and inhibits the development of Brain-associated DCs, possibly through repressing id2a expression. Our study unravels the phenotypical and functional heterogeneity of the CNS myeloid lineages and uncovers the genetic network regulating the development of these subsets.