Differential Responses of Macrophages to Salmonella enterica Serovars Enteritidis and Typhimurium

Authors: OKAMURA, MASASHI - OBIHIRO UNIV., JAPAN; Lillehoj, Hyun; RAYBOURNE, RICHARD - FDA; BABU, UMA - FDA; HECKERT, ROBERT - UNIV OF MD; SASAI, KAZUMI - OSAKA PREFECTURE UNIV.; BABA, EIICHIRO - OSAKA PREFECTURE UNIV.; LILLEHOJ, ERIK - UNIV OF MD

Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/22/2006
Publication Date: 12/22/2006
Citation: Okamura, M., Lillehoj, H.S., Raybourne, R.B., Babu, U.S., Heckert, R.A., Sasai, K., Baba, E., Lillehoj, E.P. 2006. Differential Responses of Macrophages to Salmonella enterica Serovars Enteritidis and Typhimurium. Veterinary Immunology and Immunopathology 107:327-335.

Interpretive Summary: In this paper, ARS scientists collaborated with scientists at University of Osaka in Japan to investigate host innate immunity against Salmonellosis which is a major source of human food poisoning. Epidemiological studies have indicated that Salmonella enterica serovar Enteritidis (SE) is a major source of human food poisoning through consumption of contaminated eggs and egg products. Understanding how host immune system recognizes and kills SE will facilitate the development of new control method for SE. In this study, in vitro assay system was developed to evaluate the role of SE in inducing macrophage activation. The results show that macrophages are major effectors against Salmonella infection and an underlying protective mechanism involves secretion of soluble factors called chemokines by the activated macrophages. Furthermore, different Salmonella species elicited different types of macrophage and chemokine responses and these differential host responses could explain different immunopathology associated with different Salmonella infections.

Technical Abstract: Macrophages are major effectors against Salmonella infection, and also transport bacteria between host tissues and provide a protected site for intracellular bacterial replication. We hypothesized that differences in chicken macrophage responses to Salmonella enterica serovar Enteritidis (SE) and serovar Typhimurium (ST) played a role in preferential infection of eggs by SE compared with ST. To test this hypothesis, we determined bacterial phagocytosis and intracellular viability and macrophage nitric oxide (NO) production following in vitro infection with SE or ST in the presence or absence of interferon g (IFN g). The effects of bacterial components, lipopolysaccharide (LPS), outer membrane proteins (OMP) and flagella, on NO production were also assessed. Our results showed: (1) in the presence or absence of IFN g, the percentage macrophages phagocytizing SE and ST was similar (2) the number of intracellular viable SE was significantly reduced compared with ST in the presence or absence of IFN g; (3) Increased macrophage necrosis was seen in the presence of IFN g and ST; (4) Salmonella infection acted synergistically with IFN ? in induction of nitric oxide (NO) production; and (5) in the absence of IFN g, macrophages produced significantly greater NO following treatment with SE outer membrane protein (OMP) or flagella compared with ST OMP or flagella, while in the presence of IFN ? significantly less NO was produced following treatment with SE LPS compared with ST LPS. These results suggest that differential responses of chicken macrophages to SE vs. ST may result in increased macrophage death with ST which could result in an increased inflammatory response as compared to SE.