ABSTRACT
Epithelial cells lining the colon do not normally express galanin type 1 receptors (Gal1Rs). However, subsequent to infection with enteric pathogens such as Salmonella typhimurium, the Gal1R is rapidly upregulated in colonocytes where it contributes to the excess fluid production associated with diarrhoea. Humans infected with non-typhoid Salmonella respond differently according to age: infants develop diarrhoea but not bacteraemia and survive, while the elderly become bacteraemic and die. Thus the aim of this study was to determine if age-related differences exist in response to S typhimurium infection in mice, and whether these differences are due to altered Gal1R expression. Wild-type C57BL/6J mice that were 2 and 15 months old, as well as 2-month-old Gal1R knockout mice, were infected by gavage. Young wild-type mice expressed Gal1R in response to infection, had increased colonic fluid secretion, low rates of bacteraemia and survived. In contrast, 15-month-old wild-type mice expressed fewer Gal1Rs in response to infection, had attenuated increases in colonic fluid secretion, high rates of bacteraemia and died. A similar profile was noted in 2-month-old Gal1R knockout mice. Addition of polyethylene glycol to the drinking water of 15-month-old wild-type mice increased colonic fluid secretion and reduced rates of bacteraemia to those observed in 2-month-old wild-type mice and eliminated fatalities. The difference in response to S typhimurium infection with age may be due, at least in part, to decreased Gal1R expression and decreased amounts of colonic fluid secretion.
Subject(s)
Colon , Galanin/metabolism , Intestinal Secretions/metabolism , Salmonella Infections, Animal/metabolism , Salmonella typhimurium , Age Factors , Animals , Bacteremia , Diarrhea/metabolism , Enteric Nervous System/metabolism , Galanin/analysis , Gene Expression , Immunohistochemistry , Interleukin-1beta/immunology , Mice , Mice, Inbred C57BL , Mice, Knockout , NF-kappa B/analysis , NF-kappa B/metabolism , Polyethylene Glycols/therapeutic use , Receptor, Galanin, Type 1/analysis , Receptor, Galanin, Type 1/genetics , Receptor, Galanin, Type 1/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Salmonella Infections, Animal/drug therapy , Salmonella Infections, Animal/mortality , Specific Pathogen-Free Organisms , Surface-Active Agents/therapeutic use , Tumor Necrosis Factor-alpha/immunologyABSTRACT
The ability of sera to recognise secreted macromolecules of Staphylococcus aureus was examined by ELISA and Western immunoblotting. Individual secreted proteins were also studied using both human sera and sera from rabbits immunised with secreted macromolecules. Patients sera showed a wide range of IgG antibody titres to secreted macromolecules and whole bacteria. Controls showed a significantly lower IgG response. Western immunoblotting revealed that a significant number of secreted proteins were recognised by circulating IgG antibodies. Surprisingly, both the sera from controls and from patients recognised similar macromolecules including a number of potential virulence factors. The major difference was in the IgG binding to a 16-kDa component, which was recognised by the majority of the sera from infected individuals, but only by a small number of sera from healthy controls. The higher incidence of antibodies recognising the 16 kDa component may be related to our earlier finding that the major bone resorbing component of S. aureus is a heterodimeric protein containing a 16-kDa subunit, the activity of which could be blocked by sera.
