title: Defensins Potentiate a Neutralizing Antibody Response to Enteric Viral Infection.
abstract: α-defensins are abundant antimicrobial peptides with broad, potent antibacterial, antifungal, and antiviral activities in vitro. Although their contribution to host defense against bacteria in vivo has been demonstrated, comparable studies of their antiviral activity in vivo are lacking. Using a mouse model deficient in activated α-defensins in the small intestine, we show that Paneth cell α-defensins protect mice from oral infection by a pathogenic virus, mouse adenovirus 1 (MAdV-1). Survival differences between mouse genotypes are lost upon parenteral MAdV-1 infection, strongly implicating a role for intestinal defenses in attenuating pathogenesis. Although differences in α-defensin expression impact the composition of the ileal commensal bacterial population, depletion studies using broad-spectrum antibiotics revealed no effect of the microbiota on α-defensin-dependent viral pathogenesis. Moreover, despite the sensitivity of MAdV-1 infection to α-defensin neutralization in cell culture, we observed no barrier effect due to Paneth cell α-defensin activation on the kinetics and magnitude of MAdV-1 dissemination to the brain. Rather, a protective neutralizing antibody response was delayed in the absence of α-defensins. This effect was specific to oral viral infection, because antibody responses to parenteral or mucosal ovalbumin exposure were not affected by α-defensin deficiency. Thus, α-defensins play an important role as adjuvants in antiviral immunity in vivo that is distinct from their direct antiviral activity observed in cell culture.
authors.affiliation: Department of Microbiology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Anshu P
authors.initials: AP
authors.lastname: Gounder
authors.affiliation: Department of Microbiology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Nicolle D
authors.initials: ND
authors.lastname: Myers
authors.affiliation: Department of Comparative Medicine, University of Washington, Seattle, Washington, United States of America.
authors.forename: Piper M
authors.initials: PM
authors.lastname: Treuting
authors.affiliation: Department of Microbiology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Beth A
authors.initials: BA
authors.lastname: Bromme
authors.affiliation: Department of Microbiology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Wilson
authors.affiliation: Department of Microbiology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Mayim E
authors.initials: ME
authors.lastname: Wiens
authors.affiliation: Institute of Human Virology and Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Wuyuan
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Pathology and Laboratory Medicine, Keck School of Medicine of the University of Southern California, USC Norris Cancer Center, Los Angeles, California, United States of America.
authors.forename: André J
authors.initials: AJ
authors.lastname: Ouellette
authors.affiliation: Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Katherine R
authors.initials: KR
authors.lastname: Spindler
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: William C
authors.initials: WC
authors.lastname: Parks
authors.affiliation: Department of Microbiology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Jason G
authors.initials: JG
authors.lastname: Smith
mesh_terms: D000256:Adenoviridae / Q000276:immunology*; D000257:Adenoviridae Infections / Q000276:immunology*; D000818:Animals; D000890:Anti-Infective Agents / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D023082:Defensins / Q000276:immunology*; D005260:Female; D006801:Humans; D007082:Ileum / Q000276:immunology; D007421:Intestine, Small / Q000276:immunology; D007422:Intestines / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019879:Paneth Cells / Q000276:immunology; D023084:alpha-Defensins / Q000276:immunology
chemical_list: D000890:Anti-Infective Agents; D057134:Antibodies, Neutralizing; D023082:Defensins; D023084:alpha-Defensins