Some vertebrates in the animal kingdom including salamanders and teleost fish have the astonishing ability to fully regenerate many appendages and organs throughout their lifespan. This work provides an important foundation for understanding the hematopoietic origins and education of myeloid cells recruited to, and essential for, adult tissue regeneration. Recruitment of leukocytes and limb regeneration occurs in the absence of the spleen, thus confirming the dependence of liver-derived myeloid cells in regeneration and that splenic maturation is dispensable for the education of pro-regenerative macrophages. We identified that although bidirectional trafficking of leukocytes can occur between spleen and liver tissues, the liver is the major source of leukocytes recruited to regenerating limbs. To interrogate leukocyte identity, tissue origins, and modes of recruitment, we established several transgenic axolotl hematopoietic tissue transplant models and flow cytometry protocols to study cell migration and identify the source of pro-regenerative macrophages. Unlike mammals, adult axolotls do not have functional bone marrow but instead utilize liver and spleen tissues as major sites for adult hematopoiesis. Mammalian wounds are dominated by splenic-derived monocytes that originate in the bone marrow and differentiate into macrophages within the wound. Identifying the exact hematopoietic source or reservoir of myeloid cells supporting regeneration is a necessary step in characterizing differences in macrophage phenotypes regulating scarring or regeneration across species. Amputation in the absence of macrophages results in regeneration failure and scar tissue induction. The impressive ability to regenerate whole limbs after amputation, or regenerate following cardiac injury, is critically dependent on the recruitment of (myeloid) macrophage white blood cells to the site of injury. In stark contrast, salamanders can functionally repair a range of clinically relevant tissues throughout adult life. The lack of scar-free healing and regeneration in many adult human tissues imposes severe limitations on the recovery of function after injury. Genes identified from this study provide important new resources to investigate ATV disease pathology and host-pathogen dynamics in natural populations. mexicanum and related tiger salamanders because they lack proliferative lymphocyte responses that are needed to clear highly virulent iridoviruses. We speculate that ATV may be especially lethal to A. mexicanum appears to mount a robust innate immune response, we did not observe gene expression changes indicative of lymphocyte proliferation in the spleen, which is associated with clearance of Frog 3 iridovirus in adult Xenopus. By 144 hours, we observed gene expression changes indicating host-mediated cell death, inflammation, and cytotoxicity.Īlthough A. At 24 hours, we observed transcript abundance changes for genes that are associated with phagocytosis and cytokine signaling, complement, and other general immune and defense responses. mexicanum as early as 24 hours after ATV infection. The presumptive functions of these genes suggest a robust innate immune and antiviral gene expression response is initiated by A. A total of 158 up-regulated and 105 down-regulated genes were identified across all time points using statistical and fold level criteria. We used a custom microarray gene chip to characterize gene expression responses of axolotls (Ambystoma mexicanum) to an emerging viral pathogen, Ambystoma tigrinum virus (ATV).Īt 0, 24, 72, and 144 hours post-infection, spleen and lung samples were removed for estimation of host mRNA abundance and viral load. Very little is known about the immunological responses of amphibians to pathogens that are causing global population declines.
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