Deep sequencing profiles MicroRNAs related to Aspergillus fumigatus infection in lung tissues of mice

Abstract

Background: Invasive pulmonary aspergillosis (IPA) is a severe opportunistic infection with high mortality in patients with compromised immunity. The full repertoire of microRNAs (miRNAs) involved in the regulation of IPA infection remains to be established. Methods: We established a mouse IPA model and analyzed small RNA transcriptomes in lung tissues of immunodeficient IPA mice (IPA group) and matched immunodeficient control mice (control group) through next-generation sequencing. Results: A total of 3759 known miRNAs were detected, in which 23 miRNAs were identified to be related to IPA. IPA-associated miRNAs include upregulated mmu-let-7b-3p, mmu-miR124-3p, mmu-miR21a-3p, mmu-miR29c-5p, mmu-miR3473b and mmu-miR3473e, and downregulated mmu-miR-150-3p and mmu-miR-503-5p. The expression levels of eight identified miRNAs were quantified in a validation cohort (n = 40) by qRT-PCR, and results revealed the same change patterns. MiRNA target prediction revealed that all IPA-related miRNAs possibly engage a cooperative regulation of key elements in the NF-kappa B signaling pathway. Conclusion: We conclude that deep-sequencing small RNAs can uncover miRNA pool-regulating IPA. Our results may lead to further understanding IPA pathogenesis and gain insight into the complexity and diversity of small RNA molecules that regulate immunodeficient IPA. Keywords: Invasive pulmonary aspergillosis, Mice, Small RNA deep sequencing, MicroRNA