title: Sequestration and histopathology in Plasmodium chabaudi malaria are influenced by the immune response in an organ-specific manner.
abstract: Infection with the malaria parasite, Plasmodium, is associated with a strong inflammatory response and parasite cytoadhesion (sequestration) in several organs. Here, we have carried out a systematic study of sequestration and histopathology during infection of C57Bl/6 mice with Plasmodium chabaudi AS and determined the influence of the immune response. This parasite sequesters predominantly in liver and lung, but not in the brain, kidney or gut. Histopathological changes occur in multiple organs during the acute infection, but are not restricted to the organs where sequestration takes place. Adaptive immunity, and signalling through the IFNγ receptor increased sequestration and histopathology in the liver, but not in the lung, suggesting that there are differences in the adhesion molecules and/or parasite ligands utilized and mechanisms of pathogenesis in these two organs. Exacerbation of pro-inflammatory responses during infection by deletion of the il10 gene resultsin the aggravation of damage to lung and kidney irrespective of the degree of sequestration. The immune response therefore affected both sequestration and histopathology in an organ-specific manner. P.  chabaudi AS provides a good model to investigate the influence of the host response on the sequestration and specific organ pathology, which is applicable to human malaria.
authors.affiliation: Division of Parasitology, MRC National Institute for Medical Research, London, NW7 1AA, UK.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Brugat
authors.forename: Deirdre
authors.initials: D
authors.lastname: Cunningham
authors.forename: Jan
authors.initials: J
authors.lastname: Sodenkamp
authors.forename: Stephanie
authors.initials: S
authors.lastname: Coomes
authors.forename: Mark
authors.initials: M
authors.lastname: Wilson
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Spence
authors.forename: William
authors.initials: W
authors.lastname: Jarra
authors.forename: Joanne
authors.initials: J
authors.lastname: Thompson
authors.forename: Cheryl
authors.initials: C
authors.lastname: Scudamore
authors.forename: Jean
authors.initials: J
authors.lastname: Langhorne
mesh_terms: D000825:Animal Structures / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D000818:Animals; D006651:Histocytochemistry; D008288:Malaria / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016788:Plasmodium chabaudi / Q000276:immunology*