Transcriptome analysis of bronchoalveolar lavage fluid from children with severe Mycoplasma pneumoniae pneumonia reveals novel gene expression and immunodeficiency

Abstract

BackgroundA growing number of severe Mycoplasma pneumoniae pneumonia (MPP) cases have been reported recently. However, the pathogenesis of severe MPP is not clear. In the current study, transcriptome sequencing was used to identify gene expression and alternative splicing profiles to provide insights into the pathogenesis of severe MPP.MethodsRNAs of bronchoalveolar lavage fluid (BALF) samples from three severe MPP children and three mild MPP children were analyzed respectively by deep sequencing followed by computational annotation and quantification.ResultsThe gene expression analysis revealed 14 up-regulated and 34 down-regulated genes in severe MPP children comparing to mild MPP children. The top 10 most up-regulated genes were IGHV1-69, CH17-472G23.1, ATP1B2, FCER2, MUC21, IL13, FCRLB, CLEC5A, FAM124A, and INHBA. The top 10 most down-regulated genes were OSTN-AS1, IL22RA2, COL3A1, C1orf141, IGKV2-29, RP11-731F5.2, IGHV4-4, KIRREL, DNASE1L3, and COL6A2. Clustering analysis revealed similar expression pattern of CLEC5A, IL13, FCER2, and FLT1. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed changes related to primary immunodeficiency in severe MPP children comparing to mild MPP children; the pathway involves CD19, TNFRSF13C, CD79A, and AICDA genes. Among the differentially expressed genes, significant alternative splicing events were found in FCER2 and FCRLA.ConclusionsThe current study on RNA sequencing provides novel insights into the pathogenesis of severe MPP in terms of gene expression and alternative splicing. The up-regulation of IL13, FCER2, FLT1, and CLEC5A and the down-regulation of CD79A, AICDA, CD19, and TNFRSF13C may contribute to the pathogenesis of severe MPP. The differential expressions of FCER2 and FCRLA could be due to their alternative splicing.Electronic supplementary materialThe online version of this article (doi:10.1186/s40246-017-0101-y) contains supplementary material, which is available to authorized users.

Profile of proinflammatory cytokines in children with Mycoplasma pneumoniae pneumonia

“…In order to investigate the local inflammatory response in children with SMPP, we further analyzed the expression level of proinflammatory cytokines in BALF and focused on the expression of innate immune inflammatory factors. Compared to the healthy control group, the levels of TNF-α, IFN-γ, GM-CSF, IL-1β, IL-2, IL-8, IL-36, MPO, MMP-9, NE, and sB7-H3 were significantly higher [35][36][37][38]. T lymphocytes in children with SMPP were significantly activated, and the expression levels of IL-6 and IL-10 in BALF were high [35].…”

The clinical significance of IL-6s and IL-27s in Bronchoalveolar lavage fluids from children with mycoplasma pneumoniae pneumonia

“…Bronchoscopy was performed within 3 days after hospital admission for patients with MPP and immediately after hospital admission to remove the foreign bodies in bronchus from children in control. Flexible fiber optic bronchoscopy and bronchoalveolar lavage were performed following the guidelines described previously [14] . BALFs were collected from these children and stored in -80 ℃ 5 freezer.…”

The clinical significance of IL-6s and IL-27s in Bronchoalveolar lavage fluids from children with mycoplasma pneumoniae pneumonia

“…Bronchoscopy was performed within 3 days after hospital admission for patients with MPP and immediately after hospital admission to remove the foreign bodies in bronchus from children in control. Flexible fiber optic bronchoscopy and bronchoalveolar lavage were performed following the guidelines described previously [14] . BALFs were collected from these children and stored in -80 ℃ freezer.…”