Map3k14 as a Regulator of Innate and Adaptive Immune Response during Acute Viral Infection
The replication of virus in secondary lymphoid organs is crucial for the activation of antigen-presenting cells. Balanced viral replication ensures the sufficient availability of antigens and production of cytokines, and both of which are needed for virus-specific immune activation and viral elimina...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-02-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/9/2/96 |
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| author | Thamer A. Hamdan Hilal Bhat Lamin B. Cham Tom Adomati Judith Lang Fanghui Li Ali Murtaza Cornelia Hardt Philipp A. Lang Vikas Duhan Karl S. Lang |
| author_facet | Thamer A. Hamdan Hilal Bhat Lamin B. Cham Tom Adomati Judith Lang Fanghui Li Ali Murtaza Cornelia Hardt Philipp A. Lang Vikas Duhan Karl S. Lang |
| author_sort | Thamer A. Hamdan |
| collection | DOAJ |
| description | The replication of virus in secondary lymphoid organs is crucial for the activation of antigen-presenting cells. Balanced viral replication ensures the sufficient availability of antigens and production of cytokines, and both of which are needed for virus-specific immune activation and viral elimination. Host factors that regulate coordinated viral replication are not fully understood. In the study reported here, we identified <i>Map3k14</i> as an important regulator of enforced viral replication in the spleen while performing genome-wide association studies of various inbred mouse lines in a model of lymphocytic choriomeningitis virus (LCMV) infection. When alymphoplasia mice (<i>aly/aly, Map3k14<sup>aly/aly</sup>, or Nik<sup>aly/aly</sup>)</i>, which carry a mutation in Map3k14, were infected with LCMV or vesicular stomatitis virus (VSV), they display early reductions in early viral replication in the spleen, reduced innate and adaptive immune activation, and lack of viral control. Histologically, scant B cells and the lack of CD169<sup>+</sup> macrophages correlated with reduced immune activation in <i>Map3k14<sup>aly/aly</sup></i> mice. The transfer of wildtype B cells into <i>Map3k14<sup>aly/aly</sup></i> mice repopulated CD169<sup>+</sup> macrophages, restored enforced viral replication, and resulted in enhanced immune activation and faster viral control. |
| first_indexed | 2024-04-11T11:13:14Z |
| format | Article |
| id | doaj.art-cb18706514924efda4f7fd6e5f364fdd |
| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-04-11T11:13:14Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathogens |
| spelling | doaj.art-cb18706514924efda4f7fd6e5f364fdd2022-12-22T04:27:19ZengMDPI AGPathogens2076-08172020-02-01929610.3390/pathogens9020096pathogens9020096Map3k14 as a Regulator of Innate and Adaptive Immune Response during Acute Viral InfectionThamer A. Hamdan0Hilal Bhat1Lamin B. Cham2Tom Adomati3Judith Lang4Fanghui Li5Ali Murtaza6Cornelia Hardt7Philipp A. Lang8Vikas Duhan9Karl S. Lang10Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, GermanyInstitute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, GermanyInstitute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, GermanyInstitute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, GermanyInstitute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, GermanyInstitute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, GermanyInstitute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, GermanyInstitute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, GermanyDepartment of Molecular Medicine II, Medical Faculty, Heinrich Heine University, Universitätsstrasse 1, 40225 Düsseldorf, GermanyInstitute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, GermanyInstitute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, GermanyThe replication of virus in secondary lymphoid organs is crucial for the activation of antigen-presenting cells. Balanced viral replication ensures the sufficient availability of antigens and production of cytokines, and both of which are needed for virus-specific immune activation and viral elimination. Host factors that regulate coordinated viral replication are not fully understood. In the study reported here, we identified <i>Map3k14</i> as an important regulator of enforced viral replication in the spleen while performing genome-wide association studies of various inbred mouse lines in a model of lymphocytic choriomeningitis virus (LCMV) infection. When alymphoplasia mice (<i>aly/aly, Map3k14<sup>aly/aly</sup>, or Nik<sup>aly/aly</sup>)</i>, which carry a mutation in Map3k14, were infected with LCMV or vesicular stomatitis virus (VSV), they display early reductions in early viral replication in the spleen, reduced innate and adaptive immune activation, and lack of viral control. Histologically, scant B cells and the lack of CD169<sup>+</sup> macrophages correlated with reduced immune activation in <i>Map3k14<sup>aly/aly</sup></i> mice. The transfer of wildtype B cells into <i>Map3k14<sup>aly/aly</sup></i> mice repopulated CD169<sup>+</sup> macrophages, restored enforced viral replication, and resulted in enhanced immune activation and faster viral control.https://www.mdpi.com/2076-0817/9/2/96viral infectionlymphocytic choriomeningitis virusvesicular stomatitis virusgenome-wide association studyalymphoplasia micemarginal zone |
| spellingShingle | Thamer A. Hamdan Hilal Bhat Lamin B. Cham Tom Adomati Judith Lang Fanghui Li Ali Murtaza Cornelia Hardt Philipp A. Lang Vikas Duhan Karl S. Lang Map3k14 as a Regulator of Innate and Adaptive Immune Response during Acute Viral Infection Pathogens viral infection lymphocytic choriomeningitis virus vesicular stomatitis virus genome-wide association study alymphoplasia mice marginal zone |
| title | Map3k14 as a Regulator of Innate and Adaptive Immune Response during Acute Viral Infection |
| title_full | Map3k14 as a Regulator of Innate and Adaptive Immune Response during Acute Viral Infection |
| title_fullStr | Map3k14 as a Regulator of Innate and Adaptive Immune Response during Acute Viral Infection |
| title_full_unstemmed | Map3k14 as a Regulator of Innate and Adaptive Immune Response during Acute Viral Infection |
| title_short | Map3k14 as a Regulator of Innate and Adaptive Immune Response during Acute Viral Infection |
| title_sort | map3k14 as a regulator of innate and adaptive immune response during acute viral infection |
| topic | viral infection lymphocytic choriomeningitis virus vesicular stomatitis virus genome-wide association study alymphoplasia mice marginal zone |
| url | https://www.mdpi.com/2076-0817/9/2/96 |
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