Submitted to: Molecular Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/10/2008
Publication Date: N/A
Interpretive Summary: According to a CDC report published in 2007, Salmonella enterica serovar Enteritidis (SE) accounts for 18.6% of all cases in the US. SE outbreaks have been found to be associated with the consumption of contaminated foods, such as poultry meats and egg products. The nature of immune mechanism responsible for protection still remains to be known. In this study, ARS scientists collaborated with scientists at FDA, University of Delaware and Mississippi State University to apply functional genomics technology to unravel the complex host-pathogen interaction in Salmonellosis caused by Salmonella enteritis (SE). Because macrophages play an important role in innate immunity to SE, we applied avian macrophage cDNA microarray which contains 5,000 genes associated with immunity to investigate host immune response to SE. The newly developed avian macrophage-specific cDNA microarray (AMM) has made it possible to monitor the expression of thousands of gene transcripts in SE-infected chicken macrophages. Our data showed that SE infection induced the expression of proinflammatory immune mediators, but inhibited apoptosis, antigen presentation, cytoskeleton biogenesis, differentiation, motility, signal transduction, and transcription regulation. Although the exact molecular mechanisms involved in the shutdown of a spectrum of cellular pathways remain to be elucidated, the inhibitory effects are likely accountable for the silent colonization of chicken hosts by SE. New knowledge from this study will facilitate the development of control and prevention strategies for Salmonella infection that will reduce SE contamination of poultry products.
Technical Abstract: Salmonella enterica serovar Enteritidis (SE) is a major etiologic agent of non-typhoid salmonellosis. The organisms colonize adult chicken hosts without causing overt clinical signs. The immunological mechanisms underlying the silent and persistent infection of chickens by SE are not clearly understood. Using the avian macrophage-specific microarray (AMM), we determined the host responses elicited by SE during a 24-hour course of infection. Of the 4,906 elements on AMM, 269 different transcripts exhibited significant expression changes (> 2-fold, P < 0.001) with 86 being up-regulated and 183 down-regulated. Most of the transcriptional alterations occurred at 5 hours post inoculation (hpi) with more genes being repressed than activated. SE infection strongly induced the expression of proinflammatory immune mediators, pro-survival molecules, and translation factors. In contrast, the infection suppressed the classical apoptosis pathways, cytoskeleton biogenesis, cell adhesion and migration, cell differentiation, and the initiation of cell-mediated immunity. Furthermore, the infection triggered the expression of genes encoding components of the endocytic pathway and repressed those coding for protein and ion transporters. Taken together, our data indicate that the expression of chicken macrophage genes belonging to diverse functional classes was modulated by SE. The infection was characterized by pro-survival, pro-inflammatory, anti-differentiation, and anti-migration transcriptional responses.