Gebremariam, T.; Alkhazraji, S.; Alqarihi, A.; Wiederhold, N.P.; Najvar, L.K.; Patterson, T.F.; Filler, S.G.; Ibrahim, A.S. Evaluation of Sex Differences in Murine Diabetic Ketoacidosis and Neutropenic Models of Invasive Mucormycosis. J. Fungi2021, 7, 313.
Gebremariam, T.; Alkhazraji, S.; Alqarihi, A.; Wiederhold, N.P.; Najvar, L.K.; Patterson, T.F.; Filler, S.G.; Ibrahim, A.S. Evaluation of Sex Differences in Murine Diabetic Ketoacidosis and Neutropenic Models of Invasive Mucormycosis. J. Fungi 2021, 7, 313.
Gebremariam, T.; Alkhazraji, S.; Alqarihi, A.; Wiederhold, N.P.; Najvar, L.K.; Patterson, T.F.; Filler, S.G.; Ibrahim, A.S. Evaluation of Sex Differences in Murine Diabetic Ketoacidosis and Neutropenic Models of Invasive Mucormycosis. J. Fungi2021, 7, 313.
Gebremariam, T.; Alkhazraji, S.; Alqarihi, A.; Wiederhold, N.P.; Najvar, L.K.; Patterson, T.F.; Filler, S.G.; Ibrahim, A.S. Evaluation of Sex Differences in Murine Diabetic Ketoacidosis and Neutropenic Models of Invasive Mucormycosis. J. Fungi 2021, 7, 313.
Abstract
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. Although 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.
Keywords
Rhizopus; Mucor; Mucormycosis; Murine; sex
Subject
Biology and Life Sciences, Anatomy and Physiology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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