Bactericidal Immunity to Salmonella in Africans and Mechanisms Causing Its Failure in HIV Infection.
BACKGROUND:Nontyphoidal strains of Salmonella are a leading cause of death among HIV-infected Africans. Antibody-induced complement-mediated killing protects healthy Africans against Salmonella, but increased levels of anti-lipopolysaccharide (LPS) antibodies in some HIV-infected African adults bloc...
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ftdoajarticles:oai:doaj.org/article:15d877f009da4748b7c08e2b4d933470 2023-05-15T15:14:21+02:00 Bactericidal Immunity to Salmonella in Africans and Mechanisms Causing Its Failure in HIV Infection. Yun Shan Goh Francesca Necchi Colette M O'Shaughnessy Francesca Micoli Massimiliano Gavini Stephen P Young Chisomo L Msefula Esther N Gondwe Wilson L Mandala Melita A Gordon Allan J Saul Calman A MacLennan 2016-04-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0004604 https://doaj.org/article/15d877f009da4748b7c08e2b4d933470 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4825999?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004604 https://doaj.org/article/15d877f009da4748b7c08e2b4d933470 PLoS Neglected Tropical Diseases, Vol 10, Iss 4, p e0004604 (2016) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2016 ftdoajarticles https://doi.org/10.1371/journal.pntd.0004604 2022-12-31T14:27:54Z BACKGROUND:Nontyphoidal strains of Salmonella are a leading cause of death among HIV-infected Africans. Antibody-induced complement-mediated killing protects healthy Africans against Salmonella, but increased levels of anti-lipopolysaccharide (LPS) antibodies in some HIV-infected African adults block this killing. The objective was to understand how these high levels of anti-LPS antibodies interfere with the killing of Salmonella. METHODOLOGY/PRINCIPAL FINDINGS:Sera and affinity-purified antibodies from African HIV-infected adults that failed to kill invasive S. Typhimurium D23580 were compared to sera from HIV-uninfected and HIV-infected subjects with bactericidal activity. The failure of sera from certain HIV-infected subjects to kill Salmonella was found to be due to an inherent inhibitory effect of anti-LPS antibodies. This inhibition was concentration-dependent and strongly associated with IgA and IgG2 anti-LPS antibodies (p<0.0001 for both). IgG anti-LPS antibodies, from sera of HIV-infected individuals that inhibit killing at high concentration, induced killing when diluted. Conversely, IgG, from sera of HIV-uninfected adults that induce killing, inhibited killing when concentrated. IgM anti-LPS antibodies from all subjects also induced Salmonella killing. Finally, the inhibitory effect of high concentrations of anti-LPS antibodies is seen with IgM as well as IgG and IgA. No correlation was found between affinity or avidity, or complement deposition or consumption, and inhibition of killing. CONCLUSION/SIGNIFICANCE:IgG and IgM classes of anti-S. Typhimurium LPS antibodies from HIV-infected and HIV-uninfected individuals are bactericidal, while at very high concentrations, anti-LPS antibodies of all classes inhibit in vitro killing of Salmonella. This could be due to a variety of mechanisms relating to the poor ability of IgA and IgG2 to activate complement, and deposition of complement at sites where it cannot insert in the bacterial membrane. Vaccine trials are required to understand the significance ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 10 4 e0004604 |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Yun Shan Goh Francesca Necchi Colette M O'Shaughnessy Francesca Micoli Massimiliano Gavini Stephen P Young Chisomo L Msefula Esther N Gondwe Wilson L Mandala Melita A Gordon Allan J Saul Calman A MacLennan Bactericidal Immunity to Salmonella in Africans and Mechanisms Causing Its Failure in HIV Infection. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND:Nontyphoidal strains of Salmonella are a leading cause of death among HIV-infected Africans. Antibody-induced complement-mediated killing protects healthy Africans against Salmonella, but increased levels of anti-lipopolysaccharide (LPS) antibodies in some HIV-infected African adults block this killing. The objective was to understand how these high levels of anti-LPS antibodies interfere with the killing of Salmonella. METHODOLOGY/PRINCIPAL FINDINGS:Sera and affinity-purified antibodies from African HIV-infected adults that failed to kill invasive S. Typhimurium D23580 were compared to sera from HIV-uninfected and HIV-infected subjects with bactericidal activity. The failure of sera from certain HIV-infected subjects to kill Salmonella was found to be due to an inherent inhibitory effect of anti-LPS antibodies. This inhibition was concentration-dependent and strongly associated with IgA and IgG2 anti-LPS antibodies (p<0.0001 for both). IgG anti-LPS antibodies, from sera of HIV-infected individuals that inhibit killing at high concentration, induced killing when diluted. Conversely, IgG, from sera of HIV-uninfected adults that induce killing, inhibited killing when concentrated. IgM anti-LPS antibodies from all subjects also induced Salmonella killing. Finally, the inhibitory effect of high concentrations of anti-LPS antibodies is seen with IgM as well as IgG and IgA. No correlation was found between affinity or avidity, or complement deposition or consumption, and inhibition of killing. CONCLUSION/SIGNIFICANCE:IgG and IgM classes of anti-S. Typhimurium LPS antibodies from HIV-infected and HIV-uninfected individuals are bactericidal, while at very high concentrations, anti-LPS antibodies of all classes inhibit in vitro killing of Salmonella. This could be due to a variety of mechanisms relating to the poor ability of IgA and IgG2 to activate complement, and deposition of complement at sites where it cannot insert in the bacterial membrane. Vaccine trials are required to understand the significance ... |
format |
Article in Journal/Newspaper |
author |
Yun Shan Goh Francesca Necchi Colette M O'Shaughnessy Francesca Micoli Massimiliano Gavini Stephen P Young Chisomo L Msefula Esther N Gondwe Wilson L Mandala Melita A Gordon Allan J Saul Calman A MacLennan |
author_facet |
Yun Shan Goh Francesca Necchi Colette M O'Shaughnessy Francesca Micoli Massimiliano Gavini Stephen P Young Chisomo L Msefula Esther N Gondwe Wilson L Mandala Melita A Gordon Allan J Saul Calman A MacLennan |
author_sort |
Yun Shan Goh |
title |
Bactericidal Immunity to Salmonella in Africans and Mechanisms Causing Its Failure in HIV Infection. |
title_short |
Bactericidal Immunity to Salmonella in Africans and Mechanisms Causing Its Failure in HIV Infection. |
title_full |
Bactericidal Immunity to Salmonella in Africans and Mechanisms Causing Its Failure in HIV Infection. |
title_fullStr |
Bactericidal Immunity to Salmonella in Africans and Mechanisms Causing Its Failure in HIV Infection. |
title_full_unstemmed |
Bactericidal Immunity to Salmonella in Africans and Mechanisms Causing Its Failure in HIV Infection. |
title_sort |
bactericidal immunity to salmonella in africans and mechanisms causing its failure in hiv infection. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2016 |
url |
https://doi.org/10.1371/journal.pntd.0004604 https://doaj.org/article/15d877f009da4748b7c08e2b4d933470 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 10, Iss 4, p e0004604 (2016) |
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http://europepmc.org/articles/PMC4825999?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004604 https://doaj.org/article/15d877f009da4748b7c08e2b4d933470 |
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https://doi.org/10.1371/journal.pntd.0004604 |
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PLOS Neglected Tropical Diseases |
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10 |
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4 |
container_start_page |
e0004604 |
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