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Toward a humanized mouse model of Pneumocystis pneumonia

Pneumocystis is an important opportunistic fungus that causes pneumonia in children and immunocompromised individuals. Recent genomic data show that divergence of major surface glycoproteins may confer speciation and host range selectivity. On the other hand, immune clearance between mice and humans...

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Autores principales: Dai, Guixiang, Wanek, Alanna, Eddens, Taylor, Volden, Paul, Kolls, Jay K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934868/
https://www.ncbi.nlm.nih.gov/pubmed/33491669
http://dx.doi.org/10.1172/jci.insight.139573
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author Dai, Guixiang
Wanek, Alanna
Eddens, Taylor
Volden, Paul
Kolls, Jay K.
author_facet Dai, Guixiang
Wanek, Alanna
Eddens, Taylor
Volden, Paul
Kolls, Jay K.
author_sort Dai, Guixiang
collection PubMed
description Pneumocystis is an important opportunistic fungus that causes pneumonia in children and immunocompromised individuals. Recent genomic data show that divergence of major surface glycoproteins may confer speciation and host range selectivity. On the other hand, immune clearance between mice and humans is well correlated. Thus, we hypothesized that humanize mice may provide information about human immune responses involved in controlling Pneumocystis infection. CD34-engrafted huNOG-EXL mice controlled fungal burdens to a greater extent than nonengrafted mice. Moreover, engrafted mice generated fungal-specific IgM. Fungal control was associated with a transcriptional signature that was enriched for genes associated with nonopsonic recognition of trophs (CD209) and asci (CLEC7A). These same genes were downregulated in CD4-deficient mice as well as twins with bare lymphocyte syndrome with Pneumocystis pneumonia.
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spelling pubmed-79348682021-03-09 Toward a humanized mouse model of Pneumocystis pneumonia Dai, Guixiang Wanek, Alanna Eddens, Taylor Volden, Paul Kolls, Jay K. JCI Insight Research Article Pneumocystis is an important opportunistic fungus that causes pneumonia in children and immunocompromised individuals. Recent genomic data show that divergence of major surface glycoproteins may confer speciation and host range selectivity. On the other hand, immune clearance between mice and humans is well correlated. Thus, we hypothesized that humanize mice may provide information about human immune responses involved in controlling Pneumocystis infection. CD34-engrafted huNOG-EXL mice controlled fungal burdens to a greater extent than nonengrafted mice. Moreover, engrafted mice generated fungal-specific IgM. Fungal control was associated with a transcriptional signature that was enriched for genes associated with nonopsonic recognition of trophs (CD209) and asci (CLEC7A). These same genes were downregulated in CD4-deficient mice as well as twins with bare lymphocyte syndrome with Pneumocystis pneumonia. American Society for Clinical Investigation 2021-01-25 /pmc/articles/PMC7934868/ /pubmed/33491669 http://dx.doi.org/10.1172/jci.insight.139573 Text en © 2021 Dai et al. http://creativecommons.org/licenses/by/4.0/ This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Research Article
Dai, Guixiang
Wanek, Alanna
Eddens, Taylor
Volden, Paul
Kolls, Jay K.
Toward a humanized mouse model of Pneumocystis pneumonia
title Toward a humanized mouse model of Pneumocystis pneumonia
title_full Toward a humanized mouse model of Pneumocystis pneumonia
title_fullStr Toward a humanized mouse model of Pneumocystis pneumonia
title_full_unstemmed Toward a humanized mouse model of Pneumocystis pneumonia
title_short Toward a humanized mouse model of Pneumocystis pneumonia
title_sort toward a humanized mouse model of pneumocystis pneumonia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934868/
https://www.ncbi.nlm.nih.gov/pubmed/33491669
http://dx.doi.org/10.1172/jci.insight.139573
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