Distinct functional roles of amphibian (Xenopus laevis) colony-stimulating factor-1- and interleukin-34-derived macrophages.

ABSTRACT: Although M? represent the most primordial immune cell subsets, the mechanisms governing their functional heterogeneity remain poorly defined. However, it is well established that the CSF-1 cytokine contributes to monopoiesis and to this heterogeneity, whereas the unrelated IL-34 also binds the CSF-1R toward poorly understood immunologic roles. To delineate the molecular and evolutionary basis behind vertebrate M? functional heterogeneity, we performed comprehensive transcriptional and functional studies of amphibian (Xenopus laevis) BM (in vitro) and PER (in vivo) M? derived by rXlCSF-1 and rXlIL-34. Our findings indicate that these amphibian cytokines promote morphologically and functionally distinct M? populations. M? induced by rXlCSF-1 possess more robust iNOS gene expression, are substantially more phagocytic, display greater NO responses, and exhibit enhanced bactericidal capacities. By contrast, rXlIL-34-derived M? express greater levels of Arg-1 and NADPH oxidase components and possess greater respiratory burst responses. Most notably, whereas CSF-1 M? are highly susceptible to the emerging FV3 ranavirus, rXlIL-34 M? exhibit potent antiviral activity against this pathogen, which is dependent on reactive oxygen production. This work marks an advance in our understanding of the possible mechanisms governing vertebrate M? functional heterogeneity.

SUBMITTER: Grayfer L 

PROVIDER: S-EPMC4763865 | biostudies-other | 2015 Oct

REPOSITORIES: biostudies-other