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Malaria Parasite Infection Compromises Control of Concurrent Systemic Non-typhoidal Salmonella Infection via IL-10-Mediated Alteration of Myeloid Cell Function
Non-typhoidal Salmonella serotypes (NTS) cause a self-limited gastroenteritis in immunocompetent individuals, while children with severe Plasmodium falciparum malaria can develop a life-threatening disseminated infection. This co-infection is a major source of child mortality in sub-Saharan Africa....
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006898/ https://www.ncbi.nlm.nih.gov/pubmed/24787713 http://dx.doi.org/10.1371/journal.ppat.1004049 |
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author | Lokken, Kristen L. Mooney, Jason P. Butler, Brian P. Xavier, Mariana N. Chau, Jennifer Y. Schaltenberg, Nicola Begum, Ramie H. Müller, Werner Luckhart, Shirley Tsolis, Renée M. |
author_facet | Lokken, Kristen L. Mooney, Jason P. Butler, Brian P. Xavier, Mariana N. Chau, Jennifer Y. Schaltenberg, Nicola Begum, Ramie H. Müller, Werner Luckhart, Shirley Tsolis, Renée M. |
author_sort | Lokken, Kristen L. |
collection | PubMed |
description | Non-typhoidal Salmonella serotypes (NTS) cause a self-limited gastroenteritis in immunocompetent individuals, while children with severe Plasmodium falciparum malaria can develop a life-threatening disseminated infection. This co-infection is a major source of child mortality in sub-Saharan Africa. However, the mechanisms by which malaria contributes to increased risk of NTS bacteremia are incompletely understood. Here, we report that in a mouse co-infection model, malaria parasite infection blunts inflammatory responses to NTS, leading to decreased inflammatory pathology and increased systemic bacterial colonization. Blunting of NTS-induced inflammatory responses required induction of IL-10 by the parasites. In the absence of malaria parasite infection, administration of recombinant IL-10 together with induction of anemia had an additive effect on systemic bacterial colonization. Mice that were conditionally deficient for either myeloid cell IL-10 production or myeloid cell expression of IL-10 receptor were better able to control systemic Salmonella infection, suggesting that phagocytic cells are both producers and targets of malaria parasite-induced IL-10. Thus, IL-10 produced during the immune response to malaria increases susceptibility to disseminated NTS infection by suppressing the ability of myeloid cells, most likely macrophages, to control bacterial infection. |
format | Online Article Text |
id | pubmed-4006898 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-40068982014-05-09 Malaria Parasite Infection Compromises Control of Concurrent Systemic Non-typhoidal Salmonella Infection via IL-10-Mediated Alteration of Myeloid Cell Function Lokken, Kristen L. Mooney, Jason P. Butler, Brian P. Xavier, Mariana N. Chau, Jennifer Y. Schaltenberg, Nicola Begum, Ramie H. Müller, Werner Luckhart, Shirley Tsolis, Renée M. PLoS Pathog Research Article Non-typhoidal Salmonella serotypes (NTS) cause a self-limited gastroenteritis in immunocompetent individuals, while children with severe Plasmodium falciparum malaria can develop a life-threatening disseminated infection. This co-infection is a major source of child mortality in sub-Saharan Africa. However, the mechanisms by which malaria contributes to increased risk of NTS bacteremia are incompletely understood. Here, we report that in a mouse co-infection model, malaria parasite infection blunts inflammatory responses to NTS, leading to decreased inflammatory pathology and increased systemic bacterial colonization. Blunting of NTS-induced inflammatory responses required induction of IL-10 by the parasites. In the absence of malaria parasite infection, administration of recombinant IL-10 together with induction of anemia had an additive effect on systemic bacterial colonization. Mice that were conditionally deficient for either myeloid cell IL-10 production or myeloid cell expression of IL-10 receptor were better able to control systemic Salmonella infection, suggesting that phagocytic cells are both producers and targets of malaria parasite-induced IL-10. Thus, IL-10 produced during the immune response to malaria increases susceptibility to disseminated NTS infection by suppressing the ability of myeloid cells, most likely macrophages, to control bacterial infection. Public Library of Science 2014-05-01 /pmc/articles/PMC4006898/ /pubmed/24787713 http://dx.doi.org/10.1371/journal.ppat.1004049 Text en © 2014 Lokken et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Lokken, Kristen L. Mooney, Jason P. Butler, Brian P. Xavier, Mariana N. Chau, Jennifer Y. Schaltenberg, Nicola Begum, Ramie H. Müller, Werner Luckhart, Shirley Tsolis, Renée M. Malaria Parasite Infection Compromises Control of Concurrent Systemic Non-typhoidal Salmonella Infection via IL-10-Mediated Alteration of Myeloid Cell Function |
title | Malaria Parasite Infection Compromises Control of Concurrent Systemic Non-typhoidal Salmonella Infection via IL-10-Mediated Alteration of Myeloid Cell Function |
title_full | Malaria Parasite Infection Compromises Control of Concurrent Systemic Non-typhoidal Salmonella Infection via IL-10-Mediated Alteration of Myeloid Cell Function |
title_fullStr | Malaria Parasite Infection Compromises Control of Concurrent Systemic Non-typhoidal Salmonella Infection via IL-10-Mediated Alteration of Myeloid Cell Function |
title_full_unstemmed | Malaria Parasite Infection Compromises Control of Concurrent Systemic Non-typhoidal Salmonella Infection via IL-10-Mediated Alteration of Myeloid Cell Function |
title_short | Malaria Parasite Infection Compromises Control of Concurrent Systemic Non-typhoidal Salmonella Infection via IL-10-Mediated Alteration of Myeloid Cell Function |
title_sort | malaria parasite infection compromises control of concurrent systemic non-typhoidal salmonella infection via il-10-mediated alteration of myeloid cell function |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006898/ https://www.ncbi.nlm.nih.gov/pubmed/24787713 http://dx.doi.org/10.1371/journal.ppat.1004049 |
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