Antimicrobial Immunity Macrophage and granulocyte lineage immune cells are integral to all vertebrate antimicrobial defenses. These cells are the first to recognize infiltrating pathogens and orchestrate the ensuing immune responses. Perhaps for these reasons, many pathogens have evolved to evade, thrive and disseminate within these cell types.
While the best-characterized animal model of amphibian immunity is the Xenopus laevis African clawed frog, the immune mechanisms governing frog susceptibility and resistance to pathogens (such as those contributing to their declines) remain largely undefined.
We are exploring the roles of distinct tadpole and frog macrophage and granulocyte populations in the susceptibility and immune resistance of these animals to different types of pathogens.
Cells of the Frog Innate Immune System To understand the facets of amphibian susceptibility and resistance to different pathogens, we are exploring in vitro and in vivo the cellular differentiation pathways that culminate in distinct frog immune cell subsets.
Most vertebrates possess designated sites for blood cell development such as the mammalian bone marrow or the bony fish head kidney. Until recently, the anuran (frog, toad) peripheral liver was thought to be the principal site of all blood cell development. We demonstrated that while most frog blood cell precursors reside in this sub-capsular liver, the adult frog bone marrow (but not peripheral liver) host macrophage and granulocyte precursors. We are now exploring the molecular mechanisms facilitating this adaptation.
The Chytrid Fungus & Antifungal Defenses Infections of amphibians with the Batrachochytrium dendrobatidis (Bd) chytrid fungus has culminated in devastating population declines and even extinction, with the global amphibian declines significantly compounded by this pathogen. While the host-Bd immune interactions remain poorly understood, this pathogen is now know to possess numerous mechanisms by which it modulates and evades the amphibian immune system. Because the amphibian macrophages and granulocytes are the first immune cells to encounter Bd, we are focusing our research on defining the immune outcomes to Bd detection/contact with distinct frog macrophage and granulocyte subsets. In particular, we are interested in determining which of these frog immune cell subsets contribute to combating and containing Bd and which of the subsets fall victim to the immuno-modulatory effects of this pathogen.
Ranaviruses & Antiviral Immunity Amphibian infections by Frog Virus 3 (FV3) and other ranavirus genus members are causing large-scale population die-offs, thus significantly contributing to the worldwide amphibian declines. Ranaviruses are large, icosahedral, dsDNA viruses that manifest in systemic diseases, hemorrhaging and necrotic cell death within multiple afflicted organs of their amphibian hosts. We are investigating how pre- and post-metamorphic frogs deal with these infections and what immune mechanisms tip the scales of susceptibility and resistance to these viruses. Mycobacteria & Antimicrobial immunity We established the X. laevis frog as model of vertebrate macrophage immunity to mycobacteria. We are now using in vitro and in vivo approaches to explore the molecular mechanisms conferring macrophage susceptibility and resistance to mycobacteria.
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