title: Regulation of host immune responses by modification of Salmonella virulence genes.
abstract: Modifying bacterial virulence genes to probe the nature of host immunity is mostly unexplored. Here we investigate whether host immune responses can be regulated by modification of bacterial virulence genes. In mice, attenuated Salmonella mutant strains with clinical relevance elicited differential host immune responses. Oral administration of a mutant strain with a PhoP-null phenotype promoted potent innate immune responses of macrophages that were sufficient for host defense. In contrast, administration of an Aro- mutant strain elicited stronger specific antibody and T-helper (Th)-cell responses, wherein Th1-type cells were required for clearance. Thus, genetic manipulation of bacteria may be used to broadly alter immune mechanisms that regulate attenuation within the host and to tailor host immunity to specific bacterial pathogens.
authors.affiliation: Children's Hospital Medical Center, Division of Infectious Disease, Cincinnati, Ohio 45229, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: VanCott
authors.forename: S N
authors.initials: SN
authors.lastname: Chatfield
authors.forename: M
authors.initials: M
authors.lastname: Roberts
authors.forename: D M
authors.initials: DM
authors.lastname: Hone
authors.forename: E L
authors.initials: EL
authors.lastname: Hohmann
authors.forename: D W
authors.initials: DW
authors.lastname: Pascual
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto
authors.forename: H
authors.initials: H
authors.lastname: Kiyono
authors.forename: J R
authors.initials: JR
authors.lastname: McGhee
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000917:Antibody Formation; D001426:Bacterial Proteins / Q000235:genetics; D007249:Inflammation; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012475:Salmonella / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D012481:Salmonella Infections, Animal / Q000235:genetics / Q000276:immunology*; D012486:Salmonella typhimurium / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics; D014774:Virulence / Q000235:genetics
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014157:Transcription Factors; C061064:PhoP protein, Bacteria; D007371:Interferon-gamma