Dysregulated Humoral Immunity to Nontyphoidal Salmonella in HIV-Infected African Adults

Author:

MacLennan Calman A.12,Gilchrist James J.134,Gordon Melita A.356,Cunningham Adam F.1,Cobbold Mark1,Goodall Margaret1,Kingsley Robert A.7,van Oosterhout Joep J. G.36,Msefula Chisomo L.328,Mandala Wilson L.389,Leyton Denisse L.10,Marshall Jennifer L.1,Gondwe Esther N.138,Bobat Saeeda1,López-Macías Constantino11,Doffinger Rainer12,Henderson Ian R.10,Zijlstra Eduard E.6,Dougan Gordon7,Drayson Mark T.1,MacLennan Ian C. M.1,Molyneux Malcolm E.368

Affiliation:

1. Medical Research Council Centre for Immune Regulation and Clinical Immunology Service, Institute of Biomedical Research, School of Immunity and Infection, University of Birmingham, Birmingham, UK.

2. Department of Microbiology, College of Medicine, University of Malawi, Blantyre, Malawi.

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

4. Oxford University Clinical Academic Graduate School, Medical Sciences Division, John Radcliffe Hospital, Oxford, UK.

5. Gastroenterology Unit, University of Liverpool, Liverpool, UK.

6. Department of Medicine, College of Medicine, University of Malawi, Blantyre, Malawi.

7. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.

8. Liverpool School of Tropical Medicine, Pembroke Place, University of Liverpool, Liverpool, UK.

9. Department of Biochemistry, College of Medicine, University of Malawi, Blantyre, Malawi.

10. Biosciences, School of Immunity and Infection, University of Birmingham, Birmingham, UK.

11. Medical Research Unit on Immunochemistry, Specialties Hospital, National Medical Centre “Siglo XXI,” Mexican Institute for Social Security, Mexico City, Mexico.

12. Department of Clinical Biochemistry and Immunology, Addenbrooke’s Hospital, Cambridge, UK.

Abstract

HIV and Salmonella HIV-positive individuals who are infected with nontyphoidal strains of Salmonella enterica often succumb to high morbidity and mortality. Why this is the case is unknown. MacLennan et al. (p. 508 ; see the Perspective by Moir and Fauci ) have uncovered a dysregulated antibody response to Salmonella that is the likely culprit. Sera from HIV-infected individuals do a poor job of killing S. Typhimurium, despite surprisingly elevated antibody titers. Experiments showed that HIV-infected serum inhibited the power of normal serum to kill Salmonella . Inhibition was specific to antibodies against lipopolysaccharide (LPS), a component of the cell wall of Salmonella . Hence, HIV-infected sera was able to kill Salmonella strains lacking LPS, and removing LPS immunoglobulin G from infected sera permitted Salmonella killing. Thus, not only does HIV cause defects in cell-mediated immunity but it also seems to impair humoral immunity, with severe consequences for multiple infections.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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