Importance of antibody and complement for oxidative burst and killing of invasive nontyphoidalSalmonellaby blood cells in Africans

Author:

Gondwe Esther N.123,Molyneux Malcolm E.124,Goodall Margaret3,Graham Stephen M.1256,Mastroeni Pietro7,Drayson Mark T.3,MacLennan Calman A.1389

Affiliation:

1. Malawi–Liverpool–Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre 3, Malawi;

2. Liverpool School of Tropical Medicine, Pembroke Place, University of Liverpool, Liverpool L3 5QA, United Kingdom;

3. Medical Research Council Centre for Immune Regulation and Clinical Immunology Service, Institute of Biomedical Research, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom;

4. Department of Medicine, College of Medicine, University of Malawi, Blantyre 3, Malawi;

5. Department of Paediatrics, College of Medicine, University of Malawi, Blantyre 3, Malawi;

6. Centre for International Child Health, University of Melbourne Department of Paediatrics and Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, VIC 3052, Australia;

7. Centre of Veterinary Science, University of Cambridge, Cambridge, CB3 0ES, United Kingdom;

8. Division of Medical Microbiology, School of Infection and Host Defence, University of Liverpool, Liverpool L69 3GA, United Kingdom; and

9. Department of Microbiology, College of Medicine, University of Malawi, Blantyre 3, Malawi

Abstract

Bacteremia caused by nontyphoidal strains ofSalmonellais endemic among African children. Case-fatality rates are high and antibiotic resistance increasing, but no vaccine is currently available. T cells are important for clearance ofSalmonellainfection within macrophages, but in Africa, invasiveSalmonelladisease usually manifests in the blood and affects children between 4 months and 2 y of age, when anti-Salmonellaantibody is absent. We have previously found a role for complement-fixing bactericidal antibody in protecting these children. Here we show that opsonic activity of antibody and complement is required for oxidative burst and killing ofSalmonellaby blood cells in Africans. Induction of neutrophil oxidative burst correlated with anti-SalmonellaIgG and IgM titers and C3 deposition on bacteria and was significantly lower in African children younger than 2 y compared with older children. PreopsonizingSalmonellawith immune serum overcame this deficit, indicating a requirement for antibody and/or complement. Using different opsonization procedures, both antibody and complement were found to be necessary for optimal oxidative burst, phagocytosis and killing of nontyphoidalSalmonellaby peripheral blood cells in Africans. Although most strains of African nontyphoidalSalmonellacan be killed with antibody and complement alone, phagocytes in the presence of specific antibody and complement can kill strains resistant to killing by immune serum. These findings increase the likelihood that an antibody-inducing vaccine will protect against invasive nontyphoidalSalmonelladisease in African children.

Publisher

Proceedings of the National Academy of Sciences

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