DIFFERENTIATION-DEPENDENT ANTIVIRAL CAPACITIES OF AMPHIBIAN (XENOPUS LAEVIS) MACROPHAGES
Amulya Yaparla, George Washington University
Amulya Yaparlaa and Leon Grayfera
Department of Biological Sciences, George Washington University, Washington, DC
Colony stimulating factor-1 (CSF-1) is the principal macrophage (Mφ) growth factor; indispensable to macrophage survival, proliferation and differentiation. CSF-1 binds to the CSF-1 receptor (CSF-1R), expressed on committed macrophage-lineage precursors and derivative populations. Recently, interleukine-34 (IL-34) has been identified as an alternate CSF-1R ligand and in the amphibian Xenopus laevis this cytokine gives rise to morphologically and functionally distinct Mφs to those derived by CSF-1. Notably, while the X. laevis bone marrow-derived, CSF-1-differentiated Mφs are highly susceptible to the emerging Frog Virus 3 (FV3) ranavirus, IL-34 derived Mφs are resistant to this pathogen. Since antiviral interferon (IFN) cytokines are integral to vertebrate antiviral immunity, we examined the expression of these genes in CSF-1 and IL-34 Mφs to account for their differences in antiviral capacities. IL-34 Mφs showed robust gene expression of several antiviral IFN cytokines along with their respective receptors. By contrast, CSF-1 Mφs exhibit modest IFN ligand and cognate receptor gene expression, presumably accounting for their less-effective antiviral capabilities. Cellular resistance to viral replication is controlled by a plethora of cellular mechanisms, collectively referred to as restriction factors. Interestingly, IL-34 Mφs possessed significantly greater gene expression of select restriction factors than CSF-1 Mφs. Finally, we demonstrated that IL-34 Mφ-conditioned supernatants conferred anti-FV3 protection to the virally susceptible X. laevis kidney cell line (A6). Together, this work defines the mechanisms facilitating the cogent anti-FV3 capacities of IL-34 Mφs in comparison to CSF-1 derived Mφs.