Transcriptome Analysis of Bronchoalveolar Lavage Fluid From Children With Mycoplasma pneumoniae Pneumonia Reveals Natural Killer and T Cell-Proliferation Responses.

Man Gao,Kuo Wang,Huadong Zhuang,Ruihua Lu,Fanzheng Meng,Mingyue Yang,Xiaosong Wang,Genhong Cheng

doi:10.3389/fimmu.2018.01403

Abstract

Mycoplasma pneumoniae pneumonia (MPP) is one of the most common community-acquired pneumonia; this study is to explore the immune-pathogenesis of children MPP. Next-generation transcriptome sequencing was performed on the bronchoalveolar lavage fluid cells from six children with MPP and three children with foreign body aspiration as control. Some of the results had been validated by quantitative real-time PCR in an expanded group of children. Results revealed 810 differentially expressed genes in MPP group comparing to control group, of which 412 genes including RLTPR, CARD11 and RASAL3 were upregulated. These upregulated genes were mainly enriched in mononuclear cell proliferation and signaling biological processes. Kyoto encyclopedia of genes and genomes pathway analysis revealed that hematopoietic cell linage pathway, natural killer cell-mediated cytotoxicity pathway, and T cell receptor signaling pathway were significantly upregulated in MPP children. In addition, significant alternative splicing events were found in GNLY and SLC11A1 genes, which may cause the differential expressions of these genes. Our results suggest that NK and CD8+ T cells are over activated and proliferated in MPP children; the upregulated IFNγ, PRF1, GZMB, FASL, and GNLY may play important roles in the pathogenesis of children MPP.

Highlights

Mycoplasma pneumoniae pneumonia (MPP) counts for 20–40% of community-acquired pneumonia in children and even higher during epidemics [1, 2]
We found that local proliferation responses of natural killer (NK) cells and CD8+ T cells had increased in MPP children comparing to control, which revealed that both NK cells and CD8+ T cells played important roles in the pathogenesis of children MPP
To investigate the gene changes related to the acute lung injuries of MPP children, total Ribonucleic Acid (RNA) was extracted from bronchoalveolar lavage fluid (BALF) samples of each child

Summary

Introduction

Mycoplasma pneumoniae pneumonia (MPP) counts for 20–40% of community-acquired pneumonia in children and even higher during epidemics [1, 2]. Next-generation sequencing is independent on the predetermined genome sequences, highly accurate with wide dynamic detection ranges and low background [11, 12]. Using this method, we analyzed the transcriptome of bronchoalveolar lavage fluid (BALF) from children with MPP and children with airway foreign body aspiration (FB) as control (Additional File 1: Table S1 in Supplementary Material). We found that local proliferation responses of NK cells and CD8+ T cells had increased in MPP children comparing to control, which revealed that both NK cells and CD8+ T cells played important roles in the pathogenesis of children MPP. Mycoplasma pneumoniae pneumonia (MPP) is one of the most common community-acquired pneumonia; this study is to explore the immune-pathogenesis of children MPP

Methods

Results

Conclusion