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Published online before print July 20, 2005
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* Department of Viral Diseases and Immunology, National Public Health Institute, Helsinki, Finland; and
General Microbiology, Faculty of Biosciences, University of Helsinki, Finland
1Correspondence: Department of Microbiology, National Public Health Institute, Mannerheimintie 166, FIN-00300 Helsinki, Finland. E-mail: taija.pietila{at}ktl.fi
Salmonella enterica serovar typhimurium (S. typhimurium) is an intracellular pathogen causing localized gastroenteritis in humans. Macrophages (M
s) and dendritic cells (DCs) play an important role in innate immunity against Salmonella. In this report, we have compared the consequences of infection of human Ms and DCs with wild-type S. typhimurium and an isogenic PgtE-defective strain. PgtE is an outer membrane protein hypothesized to have a role in intracellular survival of Salmonella. We observed that DCs undergo full maturation in response to Salmonella infection, as indicated by up-regulation of cell-surface marker proteins CD80, CD83, CD86, and human leukocyte antigen class II. CC chemokine ligand 5 (CCL5), CXC chemokine ligand 10, tumor necrosis factor 
, interleukin (IL)-12, and IL-18 gene expression and protein production were readily induced by Salmonella-infected Ms and DCs. CCL20 was preferentially produced by Ms, whereas DCs secreted higher levels of CCL19 as compared with Ms. DCs and Ms infected with S. typhimurium also produced high levels of interferon-
(IFN-). Cytokine neutralization and stimulation experiments suggest that the production was partly regulated by Salmonella-induced type I IFNs, IL-12, and IL-18. DC cytokine production induced by Salmonella was much higher as compared with the responses induced by Salmonella lipopolysaccharide or flagellin. Ms and DCs were capable of internalizing and harboring Salmonella for several days. S. enterica PgtE provided no survival advantage for the bacteria in human Ms or DCs. Our results demonstrate that although Ms and DCs share similar functions, they may have different roles during Salmonella infection as a result of differential production of certain chemokines and cytokines.
Key Words: innate immunity • IFN- • PgtE
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