The amphibian (Xenopus laevis) colony-stimulating factor-1 and interleukin-34-derived macrophages possess disparate pathogen recognition capacities
Autor: | Leon Grayfer, Aashish Batheja, Mattie L.S. Melnyk, Hannah Docter-Loeb, Amulya Yaparla |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Amphibian Macrophage colony-stimulating factor Immunology Ranavirus Xenopus Receptor Macrophage Colony-Stimulating Factor Xenopus Proteins 03 medical and health sciences 0302 clinical medicine Immune system biology.animal Animals Humans Receptor biology Interleukins Macrophage Colony-Stimulating Factor Macrophages Pathogen-Associated Molecular Pattern Molecules Pattern recognition receptor TLR9 Cell Differentiation biology.organism_classification Cell biology TLR2 030104 developmental biology Host-Pathogen Interactions 030215 immunology Developmental Biology |
Zdroj: | Developmental and comparative immunology. 98 |
ISSN: | 1879-0089 |
Popis: | Pathogens such as the Frog Virus 3 (FV3) ranavirus are contributing to the worldwide amphibian declines. While amphibian macrophages (Mϕs) are central to the immune defenses against these viruses, the pathogen recognition capacities of disparate amphibian Mϕ subsets remain unexplored. In turn, Mϕ differentiation and functionality are interdependent on the colony-stimulating factor-1 receptor (CSF-1R), which is ligated by colony-stimulating factor-1 (CSF-1) and the unrelated interleukin-34 (IL-34) cytokines. Notably, the Xenopus laevis frog CSF-1- and IL-34-derived Mϕs are functionally distinct, and while the CSF-1-Mϕs are more susceptible to FV3, the IL-34-Mϕs are highly resistant to this pathogen. Here, we elucidate the pathogen recognition capacities of CSF-1- and IL-34-differentiated Mϕs by evaluating their baseline transcript levels of key pathogen pattern recognition receptors (PRRs). Compared to the frog CSF-1-Mϕs, their IL-34-Mϕs exhibited greater expression of PRR genes associated with viral recognition as well as PRR genes known for recognizing bacterial pathogen-associated molecular patterns (PAMPs). By contrast, the CSF-1-Mϕs displayed greater expression of toll-like receptors (TLRs) that are absent in humans. Moreover, although the two Mϕ types possessed similar expression of most downstream PRR signaling components, they exhibited distinct outcomes upon stimulation with hallmark PAMPs, as measured by their tumor necrosis factor-alpha and interferon-7 gene expression. Remarkably, stimulation with a TLR2/6 agonist conferred FV3 resistance to the otherwise susceptible CSF-1-Mϕs while treatment with a TLR9 agonist significantly ablated the IL-34-Mϕ resistance to FV3. These changes in Mϕ-FV3 susceptibility and resistance appeared to be linked to changes in their expression of key immune genes. Greater understanding of the amphibian macrophage pathogen-recognition capacities will lend to further insights into the pathogen-associated causes of the amphibian declines. |
Databáze: | OpenAIRE |
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