Integrated analysis of lncRNA and mRNA repertoires in lung from Pneumocystis infected mice

Abstract

\n Background According to the widespread use of highly active antiretroviral therapy (HAART) to HIV patients withPneumocystis pneumonia (PCP), the incidence of PCP associated with HIV has fallen. There is an enhancement of population of HIV-negative patients with PCP, who receiving immunosuppressive therapies or genetic primary immune deficiency disorders. Most of the previous studies have concentrated on the immune cell responses in PCP individuals, the present study aimed to integrate lncRNA and mRNA expression profiles in PCP patients without HIV.\nMethods The lung tissue of WT mice and BAFF-R–/– mice were harvested at 3 weeks after infected with pneumocystis. After total RNAs being extracted, transcriptome profiling was performed following the Illumina HiSeq 3000 protocol. The microarrays and quantitative RT-PCR analysis were conducted to evaluate the lncRNA and mRNA expression profiles in WT-PCP mice and BAFF-R–/– PCP mice.\nResults Compared with the control group, 166 mRNAs were observed to be aberrantly expressed (Fold change value≥2; P <0.05) in B cell-activating factor receptor deficient (BAFF-R–/–) PCP group, including 99 up-regulated and 67 down-regulated, while there were 39 lncRNAs differently expressed in BAFF-R–/– PCP group, including 24 up-regulated and 15 down-regulated genes. In addition, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on all of the differently expressed genes and the data showed that BAFF-R deficiency played an important role in the primary and adaptive immune responses in PCP. Furthermore, the lncRNA and mRNA co-expression network was established. We noted that in the core network of lncRNA-TF (transcription factors) pairs could be classified into the categories including infection and immunity pathways.\nConclusion In summary, in this study we furtherly explored the role of mature B cells in the pathogenesis and disease progression of PCP and the data demonstrated that BAFF-R deficiency play a significant role in immune regulation in PCP population.