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Evaluation of Sex Differences in Murine Diabetic Ketoacidosis and Neutropenic Models of Invasive Mucormycosis

There is increased concern that the quality, generalizability and reproducibility of biomedical research can be influenced by the sex of animals used. We studied the differences between male and female mice in response to invasive pulmonary mucormycosis including susceptibility to infection, host im...

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Autores principales: Gebremariam, Teclegiorgis, Alkhazraji, Sondus, Alqarihi, Abdullah, Wiederhold, Nathan P., Najvar, Laura K., Patterson, Thomas F., Filler, Scott G., Ibrahim, Ashraf S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072604/
https://www.ncbi.nlm.nih.gov/pubmed/33919611
http://dx.doi.org/10.3390/jof7040313
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author Gebremariam, Teclegiorgis
Alkhazraji, Sondus
Alqarihi, Abdullah
Wiederhold, Nathan P.
Najvar, Laura K.
Patterson, Thomas F.
Filler, Scott G.
Ibrahim, Ashraf S.
author_facet Gebremariam, Teclegiorgis
Alkhazraji, Sondus
Alqarihi, Abdullah
Wiederhold, Nathan P.
Najvar, Laura K.
Patterson, Thomas F.
Filler, Scott G.
Ibrahim, Ashraf S.
author_sort Gebremariam, Teclegiorgis
collection PubMed
description There is increased concern that the quality, generalizability and reproducibility of biomedical research can be influenced by the sex of animals used. We studied the differences between male and female mice in response to invasive pulmonary mucormycosis including susceptibility to infection, host immune reaction and responses to antifungal therapy. We used diabetic ketoacidotic (DKA) or neutropenic mice infected with either Rhizopus delemar or Mucor circinelloides. The only difference detected was that when DKA mice were infected with M. circinelloides, female mice were more resistant to infection than male mice (median survival time of 5 vs. 2 days for female and male mice, respectively). However, a 100% lethality was detected among infected animals of both sexes. Treatment with either liposomal amphotericin B (L-AMB) or posaconazole (POSA) protected mice from infection and eliminated the difference seen between infected but untreated female and male mice. Treatment with L-AMB consistently outperformed POSA in prolonging survival and reducing tissue fungal burden of DKA and neutropenic mice infected with R. delemar or M. circinelloides, in both mouse sexes. While little difference was detected in cytokine levels among both sexes, mucormycosis infection in the DKA mouse model induced more inflammatory cytokines/chemokines involved in neutrophil (CXCL1) and macrophage (CXCL2) recruitment vs. uninfected mice. As expected, this inflammatory response was reduced in the neutropenic mouse model. Our studies show that there are few differences between female and male DKA or neutropenic mice infected with mucormycosis with no effect on the outcome of treatment or host immune response.
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spelling pubmed-80726042021-04-27 Evaluation of Sex Differences in Murine Diabetic Ketoacidosis and Neutropenic Models of Invasive Mucormycosis Gebremariam, Teclegiorgis Alkhazraji, Sondus Alqarihi, Abdullah Wiederhold, Nathan P. Najvar, Laura K. Patterson, Thomas F. Filler, Scott G. Ibrahim, Ashraf S. J Fungi (Basel) Article There is increased concern that the quality, generalizability and reproducibility of biomedical research can be influenced by the sex of animals used. We studied the differences between male and female mice in response to invasive pulmonary mucormycosis including susceptibility to infection, host immune reaction and responses to antifungal therapy. We used diabetic ketoacidotic (DKA) or neutropenic mice infected with either Rhizopus delemar or Mucor circinelloides. The only difference detected was that when DKA mice were infected with M. circinelloides, female mice were more resistant to infection than male mice (median survival time of 5 vs. 2 days for female and male mice, respectively). However, a 100% lethality was detected among infected animals of both sexes. Treatment with either liposomal amphotericin B (L-AMB) or posaconazole (POSA) protected mice from infection and eliminated the difference seen between infected but untreated female and male mice. Treatment with L-AMB consistently outperformed POSA in prolonging survival and reducing tissue fungal burden of DKA and neutropenic mice infected with R. delemar or M. circinelloides, in both mouse sexes. While little difference was detected in cytokine levels among both sexes, mucormycosis infection in the DKA mouse model induced more inflammatory cytokines/chemokines involved in neutrophil (CXCL1) and macrophage (CXCL2) recruitment vs. uninfected mice. As expected, this inflammatory response was reduced in the neutropenic mouse model. Our studies show that there are few differences between female and male DKA or neutropenic mice infected with mucormycosis with no effect on the outcome of treatment or host immune response. MDPI 2021-04-18 /pmc/articles/PMC8072604/ /pubmed/33919611 http://dx.doi.org/10.3390/jof7040313 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gebremariam, Teclegiorgis
Alkhazraji, Sondus
Alqarihi, Abdullah
Wiederhold, Nathan P.
Najvar, Laura K.
Patterson, Thomas F.
Filler, Scott G.
Ibrahim, Ashraf S.
Evaluation of Sex Differences in Murine Diabetic Ketoacidosis and Neutropenic Models of Invasive Mucormycosis
title Evaluation of Sex Differences in Murine Diabetic Ketoacidosis and Neutropenic Models of Invasive Mucormycosis
title_full Evaluation of Sex Differences in Murine Diabetic Ketoacidosis and Neutropenic Models of Invasive Mucormycosis
title_fullStr Evaluation of Sex Differences in Murine Diabetic Ketoacidosis and Neutropenic Models of Invasive Mucormycosis
title_full_unstemmed Evaluation of Sex Differences in Murine Diabetic Ketoacidosis and Neutropenic Models of Invasive Mucormycosis
title_short Evaluation of Sex Differences in Murine Diabetic Ketoacidosis and Neutropenic Models of Invasive Mucormycosis
title_sort evaluation of sex differences in murine diabetic ketoacidosis and neutropenic models of invasive mucormycosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072604/
https://www.ncbi.nlm.nih.gov/pubmed/33919611
http://dx.doi.org/10.3390/jof7040313
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