Gene expression response of the rat small intestine following oral Salmonella infection

Abstract

Data on the molecular response of the intestine to the food-borne pathogen Salmonella are derived from in vitro studies, whereas in vivo data are lacking. We performed an oral S. enteritidis infection study in Wistar rats to obtain insight in the in vivo response in time. Expression profiles of ileal mucosa (IM) and Peyer's patches (PP) were generated using DNA microarrays at days 1, 3, and 6 postinfection. An overview of Salmonella-regulated processes was obtained and confirmed by quantitative real-time PCR on pooled and individual samples. Salmonella-induced gene expression responses in vivo are fewer and smaller than observed in vitro, and the response develops over a longer period of time. Few effects are seen at day 1 and mainly occur in IM, suggesting the mucosa as the primary site of invasion. Later, a bigger response is observed, especially in PP. Decreased expression of anti-microbial peptides genes (in IM at day 1) suggests inhibition of this process by Salmonella. Newly identified target processes are carbohydrate transport (increased expression in IM at day 1) and phase I and phase II detoxification (decreased expression at days 3 and 6). Increase of cytokine and chemokine expression occurs at later time points, both in PP and IM. Pancreatitis-associated protein, lipocalin 2, and calprotectin, potential inflammatory marker proteins, showed induced expression from day 3 onward. We conclude that the in vivo gene expression response of the ileum to Salmonella differs to a large extent from the response seen in vitro.

Intravaginal Immunization of Mice with Recombinant Salmonella enterica Serovar Typhimurium Expressing Human Papillomavirus Type 16 Antigens as a Potential Route of Vaccination against Cervical Cancer

“…Profiling of host gene expression has also been used to examine the host immune response to Salmonella infection, in particular, in cultured host cells such as murine macrophages (59) and human intestinal epithelial cells (15), in both of which Salmonella was shown to induce numerous proinflammatory genes. It was recently shown that, in contrast to the large extent of differentially modulated genes observed in these in vitro studies, oral infection with Salmonella induces few proinflammatory gene expression changes in the rat small intestine (58). Nevertheless, the disparities between the Salmonella strains, cell lines, organs, or animals used, together with the types of genes analyzed in these studies, make direct comparison to our results difficult.…”

Intestinally Secreted C-Type Lectin Reg3b Attenuates Salmonellosis but Not Listeriosis in Mice

“…Both microbial infections of conventional mice and intestinal colonization of germ-free mice by commensals increase ileal expression of the secreted C-type lectins Reg3g and Reg3b (3,12,22,25). While Reg3g has been shown to have a bactericidal activity against Gram-positive bacteria (3), the physiological function of Reg3b remains unknown.…”

“…Reg3g and Reg3b expression was determined in the ileum because this is the area where expression is upregulated during infection of rats (22,25) and upon microbial colonization of germ-free mice (3). Frozen mucosal scrapings of the ileum were pulverized under liquid nitrogen.…”

“…Studies in rodents indicate that innate recognition of bacteria or bacterial components triggers epithelial expression of secreted C-type lectins Reg3g and Reg3b (3,12,22,25). In rodents, mucosal and fecal levels of the Reg3 protein are associated with the severity of infection (25).…”

Impact ofSalmonella entericaType III Secretion System Effectors on the Eukaryotic Host Cell

“…Genes upregulated in the human intestinal epithelial cell line HT-29 infected with S. enterica serovar Dublin for 3, 8, or 20 h, included several cytokines (G-CSF, Inhibin βA, EBI3, MIP-2α, IL-8), kinases (TKT, Eck, HEK), transcription factors (IRF-1), and HLA class I [119]. Other interesting examples of global in vitro and in vivo studies are the gene expression profiling in chicken heterophils infected with S. enterica serovar Enteritidis [120], the analysis of transcriptional responses to S. enterica serovar Choleraesuis infections in pig mesenteric lymph nodes [121], the analysis of the gene expression response of the rat small intestine following oral infection with S. enterica serovar Enteritidis [122], and the transcriptional profiles from S. enterica serovar Typhi-infected children [123]. However, the role of the T3SSs on host transcriptional responses was not investigated in these studies.…”