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

Calman MacLennan; JJ Gilchrist; MA Gordon; Adam Cunningham; Mark Cobbold; Delia Goodall; RA Kingsley; JJG van Oosterhout; CL Msefula; WL Mandala; Denisse Leyton; Jennifer Marshall; Esther Gondwe; S Bobat; C Lopez-Macias; R Doffinger; Ian Henderson; EE Zijlstra; G Dougan; Mark Drayson; Ian MacLennan; ME Molyneux

doi:10.1126/science.1180346

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

Calman MacLennan, JJ Gilchrist, MA Gordon, Adam Cunningham, Mark Cobbold, Delia Goodall, RA Kingsley, JJG van Oosterhout, CL Msefula, WL Mandala, Denisse Leyton, Jennifer Marshall, Esther Gondwe, S Bobat, C Lopez-Macias, R Doffinger, Ian Henderson, EE Zijlstra, G Dougan, Mark DraysonIan MacLennan, ME Molyneux

Immunology and Immunotherapy

Research output: Contribution to journal › Article

119 Citations (Scopus)

Abstract

Nontyphoidal Salmonellae are a major cause of life-threatening bacteremia among HIV-infected individuals. Although cell-mediated immunity controls intracellular infection, antibodies protect against Salmonella bacteremia. We report that high-titer antibodies specific for Salmonella lipopolysaccharide (LPS) are associated with a lack of Salmonella-killing in HIV-infected African adults. Killing was restored by genetically shortening LPS from the target Salmonella or removing LPS-specific antibodies from serum. Complement-mediated killing of Salmonella by healthy serum is shown to be induced specifically by antibodies against outer membrane proteins. This killing is lost when excess antibody against Salmonella LPS is added. Thus, our study indicates that impaired immunity against nontyphoidal Salmonella bacteremia in HIV infection results from excess inhibitory antibodies against Salmonella LPS, whereas serum killing of Salmonella is induced by antibodies against outer membrane proteins.

Original language	English
Pages (from-to)	508-512
Number of pages	5
Journal	Science
Volume	328
Issue number	5977
DOIs	https://doi.org/10.1126/science.1180346
Publication status	Published - 1 Apr 2010

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10.1126/science.1180346

MRC Centre For Immune Regulation (Linked to DCDF.RRAK10540) (Linked to 14810 & 14835)
Jenkinson, E. (Principal Investigator)
Medical Research Council
3/08/09 → 30/09/17
Project: Research Councils
Activities of Salmonella Flagellin: FliCing Immunity On and Off and from Th1 to Th2
Cunningham, A. (Principal Investigator)
Biotechnology & Biological Sciences Research Council
19/12/08 → 18/12/11
Project: Research Councils
A Bug in the System: How Does Salmonella Induce Novel B Cell Responses?
Cunningham, A. (Principal Investigator)
Medical Research Council
27/10/08 → 26/10/11
Project: Research Councils
The Development of Cellular Therapy for the Correction of CMV-Specific Immunodeficiency After Stem Cell Transplantation
Cobbold, M. (Principal Investigator)
Medical Research Council
1/07/03 → 31/07/09
Project: Research Councils

Cite this

MacLennan, C., Gilchrist, JJ., Gordon, MA., Cunningham, A., Cobbold, M., Goodall, D., Kingsley, RA., van Oosterhout, JJG., Msefula, CL., Mandala, WL., Leyton, D., Marshall, J., Gondwe, E., Bobat, S., Lopez-Macias, C., Doffinger, R., Henderson, I., Zijlstra, EE., Dougan, G., ... Molyneux, ME. (2010). Dysregulated Humoral Immunity to Nontyphoidal Salmonella in HIV-Infected African Adults. Science, 328(5977), 508-512. https://doi.org/10.1126/science.1180346

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title = "Dysregulated Humoral Immunity to Nontyphoidal Salmonella in HIV-Infected African Adults",

abstract = "Nontyphoidal Salmonellae are a major cause of life-threatening bacteremia among HIV-infected individuals. Although cell-mediated immunity controls intracellular infection, antibodies protect against Salmonella bacteremia. We report that high-titer antibodies specific for Salmonella lipopolysaccharide (LPS) are associated with a lack of Salmonella-killing in HIV-infected African adults. Killing was restored by genetically shortening LPS from the target Salmonella or removing LPS-specific antibodies from serum. Complement-mediated killing of Salmonella by healthy serum is shown to be induced specifically by antibodies against outer membrane proteins. This killing is lost when excess antibody against Salmonella LPS is added. Thus, our study indicates that impaired immunity against nontyphoidal Salmonella bacteremia in HIV infection results from excess inhibitory antibodies against Salmonella LPS, whereas serum killing of Salmonella is induced by antibodies against outer membrane proteins.",

author = "Calman MacLennan and JJ Gilchrist and MA Gordon and Adam Cunningham and Mark Cobbold and Delia Goodall and RA Kingsley and {van Oosterhout}, JJG and CL Msefula and WL Mandala and Denisse Leyton and Jennifer Marshall and Esther Gondwe and S Bobat and C Lopez-Macias and R Doffinger and Ian Henderson and EE Zijlstra and G Dougan and Mark Drayson and Ian MacLennan and ME Molyneux",

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doi = "10.1126/science.1180346",

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pages = "508--512",

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MacLennan, C, Gilchrist, JJ, Gordon, MA, Cunningham, A, Cobbold, M, Goodall, D, Kingsley, RA, van Oosterhout, JJG, Msefula, CL, Mandala, WL, Leyton, D, Marshall, J, Gondwe, E, Bobat, S, Lopez-Macias, C, Doffinger, R, Henderson, I, Zijlstra, EE, Dougan, G, Drayson, M, MacLennan, I & Molyneux, ME 2010, 'Dysregulated Humoral Immunity to Nontyphoidal Salmonella in HIV-Infected African Adults', Science, vol. 328, no. 5977, pp. 508-512. https://doi.org/10.1126/science.1180346

TY - JOUR

T1 - Dysregulated Humoral Immunity to Nontyphoidal Salmonella in HIV-Infected African Adults

AU - MacLennan, Calman

AU - Gilchrist, JJ

AU - Gordon, MA

AU - Cunningham, Adam

AU - Cobbold, Mark

AU - Goodall, Delia

AU - Kingsley, RA

AU - van Oosterhout, JJG

AU - Msefula, CL

AU - Mandala, WL

AU - Leyton, Denisse

AU - Marshall, Jennifer

AU - Gondwe, Esther

AU - Bobat, S

AU - Lopez-Macias, C

AU - Doffinger, R

AU - Henderson, Ian

AU - Zijlstra, EE

AU - Dougan, G

AU - Drayson, Mark

AU - MacLennan, Ian

AU - Molyneux, ME

PY - 2010/4/1

Y1 - 2010/4/1

N2 - Nontyphoidal Salmonellae are a major cause of life-threatening bacteremia among HIV-infected individuals. Although cell-mediated immunity controls intracellular infection, antibodies protect against Salmonella bacteremia. We report that high-titer antibodies specific for Salmonella lipopolysaccharide (LPS) are associated with a lack of Salmonella-killing in HIV-infected African adults. Killing was restored by genetically shortening LPS from the target Salmonella or removing LPS-specific antibodies from serum. Complement-mediated killing of Salmonella by healthy serum is shown to be induced specifically by antibodies against outer membrane proteins. This killing is lost when excess antibody against Salmonella LPS is added. Thus, our study indicates that impaired immunity against nontyphoidal Salmonella bacteremia in HIV infection results from excess inhibitory antibodies against Salmonella LPS, whereas serum killing of Salmonella is induced by antibodies against outer membrane proteins.

AB - Nontyphoidal Salmonellae are a major cause of life-threatening bacteremia among HIV-infected individuals. Although cell-mediated immunity controls intracellular infection, antibodies protect against Salmonella bacteremia. We report that high-titer antibodies specific for Salmonella lipopolysaccharide (LPS) are associated with a lack of Salmonella-killing in HIV-infected African adults. Killing was restored by genetically shortening LPS from the target Salmonella or removing LPS-specific antibodies from serum. Complement-mediated killing of Salmonella by healthy serum is shown to be induced specifically by antibodies against outer membrane proteins. This killing is lost when excess antibody against Salmonella LPS is added. Thus, our study indicates that impaired immunity against nontyphoidal Salmonella bacteremia in HIV infection results from excess inhibitory antibodies against Salmonella LPS, whereas serum killing of Salmonella is induced by antibodies against outer membrane proteins.

U2 - 10.1126/science.1180346

DO - 10.1126/science.1180346

M3 - Article

C2 - 20413503

SN - 1095-9203

VL - 328

SP - 508

EP - 512

JO - Science

JF - Science

IS - 5977

ER -

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

Abstract

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Projects

MRC Centre For Immune Regulation (Linked to DCDF.RRAK10540) (Linked to 14810 & 14835)

Activities of Salmonella Flagellin: FliCing Immunity On and Off and from Th1 to Th2

A Bug in the System: How Does Salmonella Induce Novel B Cell Responses?

The Development of Cellular Therapy for the Correction of CMV-Specific Immunodeficiency After Stem Cell Transplantation

Cite this