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.