title: Chitinase dependent control of protozoan cyst burden in the brain.
abstract: Chronic infections represent a continuous battle between the host's immune system and pathogen replication. Many protozoan parasites have evolved a cyst lifecycle stage that provides it with increased protection from environmental degradation as well as endogenous host mechanisms of attack. In the case of Toxoplasma gondii, these cysts are predominantly found in the immune protected brain making clearance of the parasite more difficult and resulting in a lifelong infection. Currently, little is known about the nature of the immune response stimulated by the presence of these cysts or how they are able to propagate. Here we establish a novel chitinase-dependent mechanism of cyst control in the infected brain. Despite a dominant Th1 immune response during Toxoplasma infection there exists a population of alternatively activated macrophages (AAMØ) in the infected CNS. These cells are capable of cyst lysis via the production of AMCase as revealed by live imaging, and this chitinase is necessary for protective immunity within the CNS. These data demonstrate chitinase activity in the brain in response to a protozoan pathogen and provide a novel mechanism to facilitate cyst clearance during chronic infections.
authors.affiliation: Division of Biomedical Sciences, University of California, Riverside, California, United States of America.
authors.forename: J Philip
authors.initials: JP
authors.lastname: Nance
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Vannella
authors.forename: Danielle
authors.initials: D
authors.lastname: Worth
authors.forename: Clément
authors.initials: C
authors.lastname: David
authors.forename: David
authors.initials: D
authors.lastname: Carter
authors.forename: Shahani
authors.initials: S
authors.lastname: Noor
authors.forename: Cedric
authors.initials: C
authors.lastname: Hubeau
authors.forename: Lori
authors.initials: L
authors.lastname: Fitz
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Lane
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Wynn
authors.forename: Emma H
authors.initials: EH
authors.lastname: Wilson
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D001927:Brain Diseases / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D002688:Chitinases / Q000276:immunology; D003560:Cysts / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology* / Q000473:pathology
chemical_list: D002688:Chitinases