The systemic immune state of super-shedder mice is characterized by a unique neutrophil-dependent blunting of TH1 responses.
Host-to-host transmission of a pathogen ensures its successful propagation and maintenance within a host population. A striking feature of disease transmission is the heterogeneity in host infectiousness. It has been proposed that within a host population, 20% of the infected hosts, termed super-she...
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1003408&type=printable |
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| author | Smita Gopinath Andrew Hotson Jennifer Johns Garry Nolan Denise Monack |
| author_facet | Smita Gopinath Andrew Hotson Jennifer Johns Garry Nolan Denise Monack |
| author_sort | Smita Gopinath |
| collection | DOAJ |
| description | Host-to-host transmission of a pathogen ensures its successful propagation and maintenance within a host population. A striking feature of disease transmission is the heterogeneity in host infectiousness. It has been proposed that within a host population, 20% of the infected hosts, termed super-shedders, are responsible for 80% of disease transmission. However, very little is known about the immune state of these super-shedders. In this study, we used the model organism Salmonella enterica serovar Typhimurium, an important cause of disease in humans and animal hosts, to study the immune state of super-shedders. Compared to moderate shedders, super-shedder mice had an active inflammatory response in both the gastrointestinal tract and the spleen but a dampened T(H)1 response specific to the secondary lymphoid organs. Spleens from super-shedder mice had higher numbers of neutrophils, and a dampened T cell response, characterized by higher levels of regulatory T cells (T(regs)), fewer T-bet(+) (T(H)1) T cells as well as blunted cytokine responsiveness. Administration of the cytokine granulocyte colony stimulating factor (G-CSF) and subsequent neutrophilia was sufficient to induce the super-shedder immune phenotype in moderate-shedder mice. Similar to super-shedders, these G-CSF-treated moderate-shedders had a dampened T(H)1 response with fewer T-bet(+) T cells and a loss of cytokine responsiveness. Additionally, G-CSF treatment inhibited IL-2-mediated TH1 expansion. Finally, depletion of neutrophils led to an increase in the number of T-bet(+) T(H)1 cells and restored their ability to respond to IL-2. Taken together, we demonstrate a novel role for neutrophils in blunting IL-2-mediated proliferation of the TH1 immune response in the spleens of mice that are colonized by high levels of S. Typhimurium in the gastrointestinal tract. |
| format | Article |
| id | doaj-art-6f0a26cf37bb4bdba4ab20da517b306d |
| institution | DOAJ |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS Pathogens |
| spelling | doaj-art-6f0a26cf37bb4bdba4ab20da517b306d2025-08-20T02:59:29ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742013-01-0196e100340810.1371/journal.ppat.1003408The systemic immune state of super-shedder mice is characterized by a unique neutrophil-dependent blunting of TH1 responses.Smita GopinathAndrew HotsonJennifer JohnsGarry NolanDenise MonackHost-to-host transmission of a pathogen ensures its successful propagation and maintenance within a host population. A striking feature of disease transmission is the heterogeneity in host infectiousness. It has been proposed that within a host population, 20% of the infected hosts, termed super-shedders, are responsible for 80% of disease transmission. However, very little is known about the immune state of these super-shedders. In this study, we used the model organism Salmonella enterica serovar Typhimurium, an important cause of disease in humans and animal hosts, to study the immune state of super-shedders. Compared to moderate shedders, super-shedder mice had an active inflammatory response in both the gastrointestinal tract and the spleen but a dampened T(H)1 response specific to the secondary lymphoid organs. Spleens from super-shedder mice had higher numbers of neutrophils, and a dampened T cell response, characterized by higher levels of regulatory T cells (T(regs)), fewer T-bet(+) (T(H)1) T cells as well as blunted cytokine responsiveness. Administration of the cytokine granulocyte colony stimulating factor (G-CSF) and subsequent neutrophilia was sufficient to induce the super-shedder immune phenotype in moderate-shedder mice. Similar to super-shedders, these G-CSF-treated moderate-shedders had a dampened T(H)1 response with fewer T-bet(+) T cells and a loss of cytokine responsiveness. Additionally, G-CSF treatment inhibited IL-2-mediated TH1 expansion. Finally, depletion of neutrophils led to an increase in the number of T-bet(+) T(H)1 cells and restored their ability to respond to IL-2. Taken together, we demonstrate a novel role for neutrophils in blunting IL-2-mediated proliferation of the TH1 immune response in the spleens of mice that are colonized by high levels of S. Typhimurium in the gastrointestinal tract.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1003408&type=printable |
| spellingShingle | Smita Gopinath Andrew Hotson Jennifer Johns Garry Nolan Denise Monack The systemic immune state of super-shedder mice is characterized by a unique neutrophil-dependent blunting of TH1 responses. PLoS Pathogens |
| title | The systemic immune state of super-shedder mice is characterized by a unique neutrophil-dependent blunting of TH1 responses. |
| title_full | The systemic immune state of super-shedder mice is characterized by a unique neutrophil-dependent blunting of TH1 responses. |
| title_fullStr | The systemic immune state of super-shedder mice is characterized by a unique neutrophil-dependent blunting of TH1 responses. |
| title_full_unstemmed | The systemic immune state of super-shedder mice is characterized by a unique neutrophil-dependent blunting of TH1 responses. |
| title_short | The systemic immune state of super-shedder mice is characterized by a unique neutrophil-dependent blunting of TH1 responses. |
| title_sort | systemic immune state of super shedder mice is characterized by a unique neutrophil dependent blunting of th1 responses |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1003408&type=printable |
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