Maternal schistosomiasis impairs offspring Interleukin-4 production and B cell expansion.
Epidemiological studies have identified a correlation between maternal helminth infections and reduced immunity to some early childhood vaccinations, but the cellular basis for this is poorly understood. Here, we investigated the effects of maternal Schistosoma mansoni infection on steady-state offs...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2021-02-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1009260&type=printable |
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| author | Diana Cortés-Selva Lisa Gibbs Andrew Ready H Atakan Ekiz Ryan O'Connell Bartek Rajwa Keke C Fairfax |
| author_facet | Diana Cortés-Selva Lisa Gibbs Andrew Ready H Atakan Ekiz Ryan O'Connell Bartek Rajwa Keke C Fairfax |
| author_sort | Diana Cortés-Selva |
| collection | DOAJ |
| description | Epidemiological studies have identified a correlation between maternal helminth infections and reduced immunity to some early childhood vaccinations, but the cellular basis for this is poorly understood. Here, we investigated the effects of maternal Schistosoma mansoni infection on steady-state offspring immunity, as well as immunity induced by a commercial tetanus/diphtheria vaccine using a dual IL-4 reporter mouse model of maternal schistosomiasis. We demonstrate that offspring born to S. mansoni infected mothers have reduced circulating plasma cells and peripheral lymph node follicular dendritic cells at steady state. These reductions correlate with reduced production of IL-4 by iNKT cells, the cellular source of IL-4 in the peripheral lymph node during early life. These defects in follicular dendritic cells and IL-4 production were maintained long-term with reduced secretion of IL-4 in the germinal center and reduced generation of TFH, memory B, and memory T cells in response to immunization with tetanus/diphtheria. Using single-cell RNASeq following tetanus/diphtheria immunization of offspring, we identified a defect in cell-cycle and cell-proliferation pathways in addition to a reduction in Ebf-1, a key B-cell transcription factor, in the majority of follicular B cells. These reductions are dependent on the presence of egg antigens in the mother, as offspring born to single-sex infected mothers do not have these transcriptional defects. These data indicate that maternal schistosomiasis leads to long-term defects in antigen-induced cellular immunity, and for the first time provide key mechanistic insight into the factors regulating reduced immunity in offspring born to S. mansoni infected mothers. |
| format | Article |
| id | doaj-art-446d0b8b30734010a24e8f897ced3428 |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2021-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-446d0b8b30734010a24e8f897ced34282025-08-20T02:00:59ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742021-02-01172e100926010.1371/journal.ppat.1009260Maternal schistosomiasis impairs offspring Interleukin-4 production and B cell expansion.Diana Cortés-SelvaLisa GibbsAndrew ReadyH Atakan EkizRyan O'ConnellBartek RajwaKeke C FairfaxEpidemiological studies have identified a correlation between maternal helminth infections and reduced immunity to some early childhood vaccinations, but the cellular basis for this is poorly understood. Here, we investigated the effects of maternal Schistosoma mansoni infection on steady-state offspring immunity, as well as immunity induced by a commercial tetanus/diphtheria vaccine using a dual IL-4 reporter mouse model of maternal schistosomiasis. We demonstrate that offspring born to S. mansoni infected mothers have reduced circulating plasma cells and peripheral lymph node follicular dendritic cells at steady state. These reductions correlate with reduced production of IL-4 by iNKT cells, the cellular source of IL-4 in the peripheral lymph node during early life. These defects in follicular dendritic cells and IL-4 production were maintained long-term with reduced secretion of IL-4 in the germinal center and reduced generation of TFH, memory B, and memory T cells in response to immunization with tetanus/diphtheria. Using single-cell RNASeq following tetanus/diphtheria immunization of offspring, we identified a defect in cell-cycle and cell-proliferation pathways in addition to a reduction in Ebf-1, a key B-cell transcription factor, in the majority of follicular B cells. These reductions are dependent on the presence of egg antigens in the mother, as offspring born to single-sex infected mothers do not have these transcriptional defects. These data indicate that maternal schistosomiasis leads to long-term defects in antigen-induced cellular immunity, and for the first time provide key mechanistic insight into the factors regulating reduced immunity in offspring born to S. mansoni infected mothers.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1009260&type=printable |
| spellingShingle | Diana Cortés-Selva Lisa Gibbs Andrew Ready H Atakan Ekiz Ryan O'Connell Bartek Rajwa Keke C Fairfax Maternal schistosomiasis impairs offspring Interleukin-4 production and B cell expansion. PLoS Pathogens |
| title | Maternal schistosomiasis impairs offspring Interleukin-4 production and B cell expansion. |
| title_full | Maternal schistosomiasis impairs offspring Interleukin-4 production and B cell expansion. |
| title_fullStr | Maternal schistosomiasis impairs offspring Interleukin-4 production and B cell expansion. |
| title_full_unstemmed | Maternal schistosomiasis impairs offspring Interleukin-4 production and B cell expansion. |
| title_short | Maternal schistosomiasis impairs offspring Interleukin-4 production and B cell expansion. |
| title_sort | maternal schistosomiasis impairs offspring interleukin 4 production and b cell expansion |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1009260&type=printable |
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