Interleukin (IL)-12 and IL-23 are key cytokines for immunity against Salmonella in humans.
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.
MacLennan
Calman
C
Medical Research Council Centre for Immune Regulation, Division of Immunity and Infection, University of Birmingham, Birmingham, Alabama, USA. cmaclennan@mlw.medcol.mw
Fieschi
Claire
C
Lammas
David A
DA
Picard
Capucine
C
Dorman
Susan E
SE
Sanal
Ozden
O
MacLennan
Jenny M
JM
Holland
Steven M
SM
Ottenhoff
Tom H M
TH
Casanova
Jean-Laurent
JL
Kumararatne
Dinakantha S
DS
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
C508840:IL23A protein, human; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D018664:Interleukin-12; D007371:Interferon-gamma