Gebremariam Teclegiorgis, Alkhazraji Sondus, Alqarihi Abdullah, Wiederhold Nathan P, Najvar Laura K, Patterson Thomas F, Filler Scott G, Ibrahim Ashraf S
The Division of Infectious Diseases, The Lundquist Institute for Biomedical Innovation at Harbor-University of California at Los Angeles (UCLA) Medical Center, Torrance, CA 90502, USA.
University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
J Fungi (Basel). 2021 Apr 18;7(4):313. doi: 10.3390/jof7040313.
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 or . The only difference detected was that when DKA mice were infected with , 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 or , 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.
人们越来越担心所使用动物的性别会影响生物医学研究的质量、普遍性和可重复性。我们研究了雄性和雌性小鼠对侵袭性肺毛霉菌病的反应差异，包括感染易感性、宿主免疫反应和对抗真菌治疗的反应。我们使用了感染了 或 的糖尿病酮症酸中毒（DKA）或中性粒细胞减少的小鼠。检测到的唯一差异是，当DKA小鼠感染 时，雌性小鼠比雄性小鼠对感染更具抵抗力（雌性和雄性小鼠的中位生存时间分别为5天和2天）。然而，在两性感染动物中均检测到100%的致死率。用两性霉素B脂质体（L-AMB）或泊沙康唑（POSA）治疗可保护小鼠免受感染，并消除了感染但未治疗的雌性和雄性小鼠之间的差异。在延长感染 或 的DKA和中性粒细胞减少小鼠的生存时间以及降低组织真菌负荷方面，L-AMB治疗始终优于POSA，无论雌雄。虽然两性之间的细胞因子水平差异不大，但与未感染小鼠相比，DKA小鼠模型中的毛霉菌病感染诱导了更多参与中性粒细胞（CXCL1）和巨噬细胞（CXCL2）募集的炎性细胞因子/趋化因子。正如预期的那样，这种炎症反应在中性粒细胞减少小鼠模型中有所降低。我们的研究表明，感染毛霉菌病的雌性和雄性DKA或中性粒细胞减少小鼠之间几乎没有差异，对治疗结果或宿主免疫反应没有影响。
