Salmonella enterica serovar Typhi (S. typhi) causes human typhoid fever, a serious and widespread disease in developing countries. Other Salmonella serovars are associated with food-borne infections. The recent emergence of multi-drug-resistant Salmonella strains highlights the need for better preventive measures, including vaccination. The available vaccines against Salmonella infection do not confer optimal protection. The design of new Salmonella vaccines must be based on the identification of suitable virulence genes and on knowledge of the immunological mechanisms of resistance to the disease. Control and clearance of a vaccine strain rely on the phagocyte oxidative burst, reactive nitrogen intermediates, inflammatory cytokines and CD4+ TCR-αβ+ T cells and are controlled by genes including NRAMP1 and MHC class II. Vaccine-induced resistance to reinfection requires the presence of Th1-type immunological memory and anti-Salmonella antibodies. The interaction between T and B cells is essential for the development of resistance following vaccination. The identification of immunodeficiencies that render individuals more susceptible to salmonellosis must be taken into consideration when designing and testing live attenuated Salmonella vaccines. An ideal live Salmonella vaccine should therefore be safe, regardless of the immunological status of the vaccinee, but still immunogenic.

Infection of mice with

SummaryImmune serum has a protective role against Salmonella infections in mice, domestic animals and humans. In this study, the effect of antibody on the interaction between murine macrophages and S. enterica serovar Typhimurium was examined. Detailed analysis at the single-cell level demonstrated that opsonization of the bacteria with immune serum enhanced bacterial uptake and altered bacterial distribution within individual phagocytic cells. Using gene-targeted mice deficient in individual Fc gamma receptors it was shown that immune serum enhanced bacterial internalization by macrophages via the high-affinity immunoglobulin G (IgG) receptor, Fc gamma receptor I. Exposure of murine macrophages to S. enterica serovar Typhimurium opsonized with immune serum resulted in increased production of superoxide, leading to enhanced antibacterial functions of the infected cells. However, opsonization of bacteria with immune serum did not increase either nitric oxide production in response to S. enterica serovar Typhimurium or fusion of phagosomes with lysosomes.

SummaryAntibodies play an important role in immunity to Salmonella enterica. Here we evaluated the requirement for Fcc receptors in host resistance to S. enterica using an in vivo model of systemic infection. We show that mice lacking FccRI, II and III can control and clear a primary infection with S. enterica micro-organisms of low virulence, but are impaired in the expression of vaccine-induced acquired immunity to oral challenge with virulent bacteria. We also show that, in vivo, FccRI, II, III )/) mice were able to mount efficient T-helper 1 type T-cell responses and antibody responses specific for S. enterica. The work indicates that targeting S. enterica to FccR is needed for the expression of vaccine-induced acquired immunity, but is not essential for the engenderment of T-and B-cell immunity to the bacterium in vivo.

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