AUTHOR=Xu Mei-nian , Li Li , Pan Wen , Zheng Huan-xin , Wang Meng-lei , Peng Xiao-ming , Dai Si-qi , Tang Ying-mei , Zeng Kang , Huang Xiao-wen 

TITLE=Zinc Oxide Nanoparticles Prime a Protective Immune Response in Galleria mellonella to Defend Against Candida albicans

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.766138

DOI=10.3389/fmicb.2021.766138

ISSN=1664-302X

ABSTRACT=<p><bold>Purpose:</bold> Zinc oxide nanoparticles (ZnO-NPs) have exerted antimicrobial properties. However, there is insufficient evaluation regarding the <italic>in vivo</italic> antifungal activity of ZnO-NPs. This study aimed to investigate the efficacy and mechanism of ZnO-NPs in controlling <italic>Candida albicans</italic> in the invertebrate <italic>Galleria mellonella</italic>.</p><p><bold>Methods:</bold><italic>Galleria mellonella</italic> larvae were injected with different doses of ZnO-NPs to determine their <italic>in vivo</italic> toxicity. Non-toxic doses of ZnO-NPs were chosen for prophylactic injection in <italic>G. mellonella</italic> followed by <italic>C. albicans</italic> infection. Then the direct <italic>in vitro</italic> antifungal effect of ZnO-NPs against <italic>C. albicans</italic> was evaluated. In addition, the mode of action of ZnO-NPs was assessed in larvae through different assays: quantification of hemocyte density, morphology observation of hemocytes, characterization of hemocyte aggregation and phagocytosis, and measurement of hemolymph phenoloxidase (PO) activity.</p><p><bold>Results:</bold> Zinc oxide nanoparticles were non-toxic to the larvae at relatively low concentrations (≤20 mg/kg). ZnO-NP pretreatment significantly prolonged the survival of <italic>C. albicans-</italic>infected larvae and decreased the fungal dissemination and burden in the <italic>C. albicans-</italic>infected larvae. This observation was more related to the activation of host defense rather than their fungicidal capacities. Specifically, ZnO-NP treatment increased hemocyte density, promoted hemocyte aggregation, enhanced hemocyte phagocytosis, and activated PO activity in larvae.</p><p><bold>Conclusion:</bold> Prophylactic treatment with lower concentrations of ZnO-NPs protects <italic>G. mellonella</italic> from <italic>C. albicans</italic> infection. The innate immune response primed by ZnO-NPs may be part of the reason for the protective effects. This study provides new evidence of the capacity of ZnO-NPs in enhancing host immunity and predicts that ZnO-NPs will be attractive for further anti-infection applications.</p>