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....
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-05-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1004049&type=printable |
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| author | Kristen L Lokken Jason P Mooney Brian P Butler Mariana N Xavier Jennifer Y Chau Nicola Schaltenberg Ramie H Begum Werner Müller Shirley Luckhart Renée M Tsolis |
| author_facet | Kristen L Lokken Jason P Mooney Brian P Butler Mariana N Xavier Jennifer Y Chau Nicola Schaltenberg Ramie H Begum Werner Müller Shirley Luckhart Renée M Tsolis |
| author_sort | Kristen L Lokken |
| collection | DOAJ |
| 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 | Article |
| id | doaj-art-fa3a233f61834e62bf9cd43453497023 |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2014-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-fa3a233f61834e62bf9cd434534970232025-08-20T02:14:41ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742014-05-01105e100404910.1371/journal.ppat.1004049Malaria parasite infection compromises control of concurrent systemic non-typhoidal Salmonella infection via IL-10-mediated alteration of myeloid cell function.Kristen L LokkenJason P MooneyBrian P ButlerMariana N XavierJennifer Y ChauNicola SchaltenbergRamie H BegumWerner MüllerShirley LuckhartRenée M TsolisNon-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.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1004049&type=printable |
| spellingShingle | Kristen L Lokken Jason P Mooney Brian P Butler Mariana N Xavier Jennifer Y Chau Nicola Schaltenberg Ramie H Begum Werner Müller Shirley Luckhart Renée M Tsolis Malaria parasite infection compromises control of concurrent systemic non-typhoidal Salmonella infection via IL-10-mediated alteration of myeloid cell function. PLoS Pathogens |
| 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 |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1004049&type=printable |
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