A perspective into the relationships between amphibian ( Xenopus laevis ) myeloid cell subsets.

Macrophage (M ϕ )-lineage cells are integral to the immune defences of all vertebrates, including amphibians. Across vertebrates, M ϕ differentiation and functionality depend on activation of the colony stimulating factor-1 (CSF1) receptor by CSF1 and interluekin-34 (IL34) cytokines. Our findings to date indicate that amphibian ( Xenopus laevis ) M ϕ s differentiated with CSF1 and IL34 are morphologically, transcriptionally and functionally distinct. Notably, mammalian M ϕ s share common progenitor population(s) with dendritic cells (DCs), which rely on fms-like tyrosine kinase 3 ligand (FLT3L) for differentiation while X. laevis IL34-M ϕ s exhibit many features attributed to mammalian DCs. Presently, we compared X. laevis CSF1- and IL34-M ϕ s with FLT3L-derived X. laevis DCs. Our transcriptional and functional analyses indicated that indeed the frog IL34-M ϕ s and FLT3L-DCs possessed many commonalities over CSF1-M ϕ s, including transcriptional profiles and functional capacities. Compared to X. laevis CSF1-M ϕ s, the IL34-M ϕ s and FLT3L-DCs possess greater surface major histocompatibility complex (MHC) class I, but not MHC class II expression, were better at eliciting mixed leucocyte responses in vitro and generating in vivo re-exposure immune responses against Mycobacterium marinum . Further analyses of non-mammalian myelopoiesis akin to those described here, will grant unique perspectives into the evolutionarily retained and diverged pathways of M ϕ and DC functional differentiation. This article is part of the theme issue 'Amphibian immunity: stress, disease and ecoimmunology'.