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

Macrophage (Mϕ)-lineage cells are integral to the immune defences of all vertebrates, including amphibians. Across vertebrates, Mϕ 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) Mϕs differentiated with CSF1 and IL34 are morphologically, transcriptionally and functionally distinct. Notably, mammalian Mϕs 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-Mϕs exhibit many features attributed to mammalian DCs. Presently, we compared X. laevis CSF1- and IL34-Mϕs with FLT3L-derived X. laevis DCs. Our transcriptional and functional analyses indicated that indeed the frog IL34-Mϕs and FLT3L-DCs possessed many commonalities over CSF1-Mϕs, including transcriptional profiles and functional capacities. Compared to X. laevis CSF1-Mϕs, the IL34-Mϕs 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 Mϕ and DC functional differentiation. This article is part of the theme issue 'Amphibian immunity: stress, disease and ecoimmunology'.