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

被引:8
作者
Gebremariam, Teclegiorgis [1 ]
Alkhazraji, Sondus [1 ]
Alqarihi, Abdullah [1 ]
Wiederhold, Nathan P. [2 ]
Najvar, Laura K. [2 ,3 ]
Patterson, Thomas E. [2 ,3 ]
Filler, Scott G. [1 ,4 ]
Ibrahim, Ashraf S. [1 ,4 ]
机构
[1] Univ Calif Los Angeles UCLA, Div Infect Dis, Lundquist Inst Biomed Innovat Harbor, Torrance, CA 90502 USA
[2] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA
[3] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA
[4] UCLA, David Geffen Sch Med, Los Angeles, CA 90095 USA
关键词
Rhizopus; Mucor; mucormycosis; murine; sex; AMPHOTERICIN-B; RHIZOPUS-ORYZAE; POSACONAZOLE; CELL; VORICONAZOLE; PROPHYLAXIS; RECRUITMENT; FLUCONAZOLE; ZYGOMYCOSIS; ESTROGENS;
D O I
10.3390/jof7040313
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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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页数:10
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