title: Interleukin (IL)-12 and IL-23 are key cytokines for immunity against Salmonella in humans.
abstract: Patients with inherited deficiency of the interleukin (IL)-12/IL-23-interferon (IFN)- gamma axis show increased susceptibility to invasive disease caused by the intramacrophage pathogens salmonellae and mycobacteria. We analyzed data on 154 patients with such deficiency. Significantly more patients with IL-12/IL-23-component deficiency had a history of salmonella disease than did those with IFN- gamma -component deficiency. Salmonella disease was typically severe, extraintestinal, and caused by nontyphoidal serovars. These findings strongly suggest that IL-12/IL-23 is a key cytokine for immunity against salmonella in humans and that IL-12/IL-23 mediates this protective effect partly through IFN- gamma -independent pathways. Investigation of the IL-12/IL-23-IFN- gamma axis should be considered in patients with invasive salmonella disease.
authors.affiliation: Medical Research Council Centre for Immune Regulation, Division of Immunity and Infection, University of Birmingham, Birmingham, Alabama, USA. cmaclennan@mlw.medcol.mw
authors.forename: Calman
authors.initials: C
authors.lastname: MacLennan
authors.forename: Claire
authors.initials: C
authors.lastname: Fieschi
authors.forename: David A
authors.initials: DA
authors.lastname: Lammas
authors.forename: Capucine
authors.initials: C
authors.lastname: Picard
authors.forename: Susan E
authors.initials: SE
authors.lastname: Dorman
authors.forename: Ozden
authors.initials: O
authors.lastname: Sanal
authors.forename: Jenny M
authors.initials: JM
authors.lastname: MacLennan
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
authors.forename: Tom H M
authors.initials: TH
authors.lastname: Ottenhoff
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
authors.forename: Dinakantha S
authors.initials: DS
authors.lastname: Kumararatne
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology*; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012475:Salmonella / Q000276:immunology*; D012480:Salmonella Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology
chemical_list: C508840:IL23A protein, human; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D018664:Interleukin-12; D007371:Interferon-gamma