title: Macrophages mediate flagellin induced inflammasome activation and host defense in zebrafish.
abstract: The inflammasome is an innate immune complex whose rapid inflammatory outputs play a critical role in controlling infection; however, the host cells that mediate inflammasome responses in vivo are not well defined. Using zebrafish larvae, we examined the cellular immune responses to inflammasome activation during infection. We compared the host responses with two Listeria monocytogenes strains: wild type and Lm-pyro, a strain engineered to activate the inflammasome via ectopic expression of flagellin. Infection with Lm-pyro led to activation of the inflammasome, macrophage pyroptosis and ultimately attenuation of virulence. Depletion of caspase A, the zebrafish caspase-1 homolog, restored Lm-pyro virulence. Inflammasome activation specifically recruited macrophages to infection sites, whereas neutrophils were equally recruited to wild type and Lm-pyro infections. Similar to caspase A depletion, macrophage deficiency rescued Lm-pyro virulence to wild-type levels, while defective neutrophils had no specific effect. Neutrophils were, however, important for general clearance of L. monocytogenes, as both wild type and Lm-pyro were more virulent in larvae with defective neutrophils. This study characterizes a novel model for inflammasome studies in an intact host, establishes the importance of macrophages during inflammasome responses and adds importance to the role of neutrophils in controlling L. monocytogenes infections.
authors.affiliation: Microbiology Doctoral Training Program, University of Wisconsin-Madison, Madison, Wisconsin, 53706, USA.|Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, Wisconsin, 53706, USA.
authors.forename: William J B
authors.initials: WJ
authors.lastname: Vincent
authors.affiliation: Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, Wisconsin, 53706, USA.|Department of Pediatrics, University of Wisconsin-Madison, Madison, Wisconsin, 53706, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Freisinger
authors.affiliation: Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, Wisconsin, 53706, USA.
authors.forename: Pui-Ying
authors.initials: PY
authors.lastname: Lam
authors.affiliation: Microbiology Doctoral Training Program, University of Wisconsin-Madison, Madison, Wisconsin, 53706, USA.|Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, Wisconsin, 53706, USA.|Department of Pediatrics, University of Wisconsin-Madison, Madison, Wisconsin, 53706, USA.|Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, Wisconsin, 53706, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Huttenlocher
authors.affiliation: Microbiology Doctoral Training Program, University of Wisconsin-Madison, Madison, Wisconsin, 53706, USA.|Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, Wisconsin, 53706, USA.
authors.forename: John-Demian
authors.initials: JD
authors.lastname: Sauer
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005408:Flagellin / Q000276:immunology*; D058847:Inflammasomes / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D000069292:Pyroptosis; D015027:Zebrafish / Q000276:immunology*
chemical_list: D058847:Inflammasomes; D005408:Flagellin