Cargando…
Vaccine Protection of Mice With Primary Immunodeficiencies Against Disseminated Coccidioidomycosis
Disseminated coccidioidomycosis (DCM), often a severe and refractory disease leading to poor outcomes, is a risk for people with certain primary immunodeficiencies (PID). Several DCM-associated PID (STAT4, STAT3, IFNγ, and Dectin-1) are modeled in mice. To determine if vaccination could provide thes...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8777018/ https://www.ncbi.nlm.nih.gov/pubmed/35071044 http://dx.doi.org/10.3389/fcimb.2021.790488 |
_version_ | 1784636966585761792 |
---|---|
author | Powell, Daniel A. Hsu, Amy P. Butkiewicz, Christine D. Trinh, Hien T. Frelinger, Jeffrey A. Holland, Steven M. Galgiani, John N. Shubitz, Lisa F. |
author_facet | Powell, Daniel A. Hsu, Amy P. Butkiewicz, Christine D. Trinh, Hien T. Frelinger, Jeffrey A. Holland, Steven M. Galgiani, John N. Shubitz, Lisa F. |
author_sort | Powell, Daniel A. |
collection | PubMed |
description | Disseminated coccidioidomycosis (DCM), often a severe and refractory disease leading to poor outcomes, is a risk for people with certain primary immunodeficiencies (PID). Several DCM-associated PID (STAT4, STAT3, IFNγ, and Dectin-1) are modeled in mice. To determine if vaccination could provide these mice protection, mice with mutations in Stat4, Stat3, Ifngr1, Clec7a (Dectin-1), and Rag-1 (T- and B-cell deficient) knockout (KO) mice were vaccinated with the live, avirulent, Δcps1 vaccine strain and subsequently challenged intranasally with pathogenic Coccidioides posadasii Silveira strain. Two weeks post-infection, vaccinated mice of all strains except Rag-1 KO had significantly reduced lung and spleen fungal burdens (p<0.05) compared to unvaccinated control mice. Splenic dissemination was prevented in most vaccinated immunodeficient mice while all unvaccinated B6 mice and the Rag-1 KO mice displayed disseminated disease. The mitigation of DCM by Δcps1 vaccination in these mice suggests that it could also benefit humans with immunogenetic risks of severe disease. |
format | Online Article Text |
id | pubmed-8777018 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87770182022-01-22 Vaccine Protection of Mice With Primary Immunodeficiencies Against Disseminated Coccidioidomycosis Powell, Daniel A. Hsu, Amy P. Butkiewicz, Christine D. Trinh, Hien T. Frelinger, Jeffrey A. Holland, Steven M. Galgiani, John N. Shubitz, Lisa F. Front Cell Infect Microbiol Cellular and Infection Microbiology Disseminated coccidioidomycosis (DCM), often a severe and refractory disease leading to poor outcomes, is a risk for people with certain primary immunodeficiencies (PID). Several DCM-associated PID (STAT4, STAT3, IFNγ, and Dectin-1) are modeled in mice. To determine if vaccination could provide these mice protection, mice with mutations in Stat4, Stat3, Ifngr1, Clec7a (Dectin-1), and Rag-1 (T- and B-cell deficient) knockout (KO) mice were vaccinated with the live, avirulent, Δcps1 vaccine strain and subsequently challenged intranasally with pathogenic Coccidioides posadasii Silveira strain. Two weeks post-infection, vaccinated mice of all strains except Rag-1 KO had significantly reduced lung and spleen fungal burdens (p<0.05) compared to unvaccinated control mice. Splenic dissemination was prevented in most vaccinated immunodeficient mice while all unvaccinated B6 mice and the Rag-1 KO mice displayed disseminated disease. The mitigation of DCM by Δcps1 vaccination in these mice suggests that it could also benefit humans with immunogenetic risks of severe disease. Frontiers Media S.A. 2022-01-07 /pmc/articles/PMC8777018/ /pubmed/35071044 http://dx.doi.org/10.3389/fcimb.2021.790488 Text en Copyright © 2022 Powell, Hsu, Butkiewicz, Trinh, Frelinger, Holland, Galgiani and Shubitz https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cellular and Infection Microbiology Powell, Daniel A. Hsu, Amy P. Butkiewicz, Christine D. Trinh, Hien T. Frelinger, Jeffrey A. Holland, Steven M. Galgiani, John N. Shubitz, Lisa F. Vaccine Protection of Mice With Primary Immunodeficiencies Against Disseminated Coccidioidomycosis |
title | Vaccine Protection of Mice With Primary Immunodeficiencies Against Disseminated Coccidioidomycosis |
title_full | Vaccine Protection of Mice With Primary Immunodeficiencies Against Disseminated Coccidioidomycosis |
title_fullStr | Vaccine Protection of Mice With Primary Immunodeficiencies Against Disseminated Coccidioidomycosis |
title_full_unstemmed | Vaccine Protection of Mice With Primary Immunodeficiencies Against Disseminated Coccidioidomycosis |
title_short | Vaccine Protection of Mice With Primary Immunodeficiencies Against Disseminated Coccidioidomycosis |
title_sort | vaccine protection of mice with primary immunodeficiencies against disseminated coccidioidomycosis |
topic | Cellular and Infection Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8777018/ https://www.ncbi.nlm.nih.gov/pubmed/35071044 http://dx.doi.org/10.3389/fcimb.2021.790488 |
work_keys_str_mv | AT powelldaniela vaccineprotectionofmicewithprimaryimmunodeficienciesagainstdisseminatedcoccidioidomycosis AT hsuamyp vaccineprotectionofmicewithprimaryimmunodeficienciesagainstdisseminatedcoccidioidomycosis AT butkiewiczchristined vaccineprotectionofmicewithprimaryimmunodeficienciesagainstdisseminatedcoccidioidomycosis AT trinhhient vaccineprotectionofmicewithprimaryimmunodeficienciesagainstdisseminatedcoccidioidomycosis AT frelingerjeffreya vaccineprotectionofmicewithprimaryimmunodeficienciesagainstdisseminatedcoccidioidomycosis AT hollandstevenm vaccineprotectionofmicewithprimaryimmunodeficienciesagainstdisseminatedcoccidioidomycosis AT galgianijohnn vaccineprotectionofmicewithprimaryimmunodeficienciesagainstdisseminatedcoccidioidomycosis AT shubitzlisaf vaccineprotectionofmicewithprimaryimmunodeficienciesagainstdisseminatedcoccidioidomycosis |