title: CRIg mediates early Kupffer cell responses to adenovirus.
abstract: Whereas adenoviral vectors are known to activate the complement cascade, leading to fixation of C3 proteins to the viral capsid, the consequences of this activation for viral clearance from the circulation are not known. Liver KCs, the macrophage population responsible for early uptake and elimination of many blood-borne pathogens, express CRIg, a complement receptor for C3 proteins. Here, we find that CRIg is important for the early elimination of C3-coated adenoviral vectors from the sinusoidal bloodstream by KCs. We further demonstrate that by acting as a critical receptor for adenovirus phagocytosis, CRIg plays an important role in regulating virus-induced KC death and depletion of these cells from the liver sinusoidal lumen. Our study thus identifies a critical pathway regulating KC function and survival in response to systemic viral infection.
authors.affiliation: Department of Immunology, Genentech, South San Francisco, California 94080, USA.
authors.forename: Jeannie Q
authors.initials: JQ
authors.lastname: He
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Katschke
authors.forename: Peter
authors.initials: P
authors.lastname: Gribling
authors.forename: Eric
authors.initials: E
authors.lastname: Suto
authors.forename: Wyne P
authors.initials: WP
authors.lastname: Lee
authors.forename: Lauri
authors.initials: L
authors.lastname: Diehl
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Eastham-Anderson
authors.forename: Anusha
authors.initials: A
authors.lastname: Ponakala
authors.forename: Laszlo
authors.initials: L
authors.lastname: Komuves
authors.forename: Jackson G
authors.initials: JG
authors.lastname: Egen
authors.forename: Menno
authors.initials: M
authors.lastname: van Lookeren Campagne
mesh_terms: D000256:Adenoviridae / Q000276:immunology* / Q000502:physiology; D000257:Adenoviridae Infections / Q000276:immunology / Q000821:virology; D000818:Animals; D016923:Cell Death; D003167:Complement Activation; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007728:Kupffer Cells / Q000166:cytology* / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D011951:Receptors, Complement / Q000276:immunology* / Q000378:metabolism*
chemical_list: D011951:Receptors, Complement; C509992:VSIG4 protein, mouse