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

Gao, Man; Kuo, Way; Yang, Mengxuan; Meng, Fanzheng; Lu, Ruipeng; Zhuang, Huadong; Cheng, Genhong; Wang, Xiaosong

doi:10.3389/fimmu.2018.01403

Cited by 27 publications

(28 citation statements)

References 48 publications

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“…First, because the children in FB control group are significantly younger than that of the MPP groups, they are not perfect controls. Although we didn’t see difference in cell composition between the groups 29 , immune response types may change as the children grow. The lack of a healthy pediatric control group because of ethical reasons does raise the question whether age affects the experimental results.…”

Section: Discussionmentioning

confidence: 61%

Cytokine signatures associate with disease severity in children with Mycoplasma pneumoniae pneumonia

Yang

Meng

Gao

et al. 2019

Sci Rep

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Host immune response may be involved in the pathogenesis of children Mycoplasma pneumoniae pneumonia (MPP). In the current study, we investigated the alterations of cytokines levels among control, mild MPP and severe MPP children to determine whether cytokine signatures associate with MPP and correlate with disease severity. We measured 13 cytokines in bronchoalveolar lavage fluid (BALF) of 88 children with MPP and 26 children with foreign body aspiration (FB) using a Luminex system. Linear discriminant analyses were performed to develop predictive models of mild MPP and severe MPP on these children. We observed nearly complete separations of severe MPP group, mild MPP group and control group in linear discriminant analyses. Eleven cytokines significantly increased in children with MPP, and seven cytokines had statistically significant upward linear trends correlated with MPP severity. In addition, compared to control group, both IFNγ/IL4 ratio and IFNγ/IL13 ratio increased in mild MPP and severe MPP groups. Our results suggest that children MPP can alter BALF cytokines signatures which associate with disease severity and can be characterized by a distinct airway molecular phenotype that has elevated Th1/Th2 ratios.

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Section: Discussionmentioning

confidence: 61%

Cytokine signatures associate with disease severity in children with Mycoplasma pneumoniae pneumonia

Yang

Meng

Gao

et al. 2019

Sci Rep

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“…Overall, based on DEGs, 32 pathways (38%) overlap between the upper and lower airways, and 27 pathways were common to all three phenotypes (OM, CRS, and Lower; Supplementary Figure 5; Supplementary Table 5). Notably about half of these 27 pathways that were common in OM, CRS, and Lower also overlap with DEGs identified in previous microarray and RNA-Seq studies (Liu et al, 2004;Kwon et al, 2006;Lee et al, 2006;Payne et al, 2008;Raju et al, 2008;Stankovic et al, 2008;Rostkowska-Nadolska et al, 2011;Klenke et al, 2012;Macias et al, 2013;Wang et al, 2016;Ramakrishnan et al, 2017;Wang et al, 2017;Gao et al, 2018a;Gao et al, 2018b;Kato et al, 2018;Langelier et al, 2018;Ninomiya et al, 2018;Okada et al, 2018;Jovanovic et al, 2019;Walter et al, 2019;Yao et al, 2019). The common pathways from Part 2 RNA-Seq data that were identified in the transcriptome literature are apoptosis, cell adhesion, cell cycle, cell proliferation, chromatin organization/remodeling, Table 6).…”

Section: Genes and Pathways Identified By Rna-seq (Part 2)mentioning

confidence: 73%

Identification of Novel Genes and Biological Pathways That Overlap in Infectious and Nonallergic Diseases of the Upper and Lower Airways Using Network Analyses

et al. 2020

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Previous genetic studies on susceptibility to otitis media and airway infections have focused on immune pathways acting within the local mucosal epithelium, and outside of allergic rhinitis and asthma, limited studies exist on the overlaps at the gene, pathway or network level between the upper and lower airways. In this report, we compared [1] pathways identified from network analysis using genes derived from published genomewide family-based and association studies for otitis media, sinusitis, and lung phenotypes, to [2] pathways identified using differentially expressed genes from RNA-sequence data from lower airway, sinus, and middle ear tissues, in particular cholesteatoma tissue compared to middle ear mucosa. For otitis media, a large number of genes (n = 1,806) were identified as differentially expressed between cholesteatoma and middle ear mucosa, which in turn led to the identification of 68 pathways that are enriched in cholesteatoma. Two differentially expressed genes CR1 and SAA1 overlap in middle ear, sinus, and lower airway samples and are potentially novel genes for otitis media susceptibility. In addition, 56 genes were differentially expressed in both tissues from the middle ear and either sinus or lower airways. Pathways that are common in upper and lower airway diseases, whether from published DNA studies or from our RNA-sequencing analyses, include chromatin organization/remodeling, endocytosis, immune system process, protein folding, and viral process. Taken together, our findings from genetic susceptibility and differential tissue expression studies support the hypothesis that the unified airway theory wherein the upper and lower respiratory tracts act as an integrated unit also applies to infectious and nonallergic airway epithelial disease. Our results may be

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“…Mycoplasma pneumoniae pneumonia (MPP) caused by Mycoplasma pneumoniae ( M. pneumoniae ) infection is one of the most common forms of community-acquired pneumonia (CAP) in children (Wang et al, 2005; Gao et al, 2018). Although M. pneumoniae infection is usually considered as a self-limited process, sometimes it may cause various severe complications such as arthritis and necrotizing pneumonia (Zhang et al, 2016; Barreira et al, 2009; Azumagawa et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

High co-expression of TNF-α and CARDS toxin is a good predictor for refractory Mycoplasma pneumoniae pneumonia

Fan

Wang

et al. 2019

Mol Med

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Background Early distinction between refractory M. pneumoniae pneumonia (RMPP) and non-RMPP (NRMPP) is still difficult. The community-acquired respiratory distress syndrome (CARDS) toxin can induce inflammatory and histopathological phenotypes associated with M. pneumoniae infection. This study aimed to investigate the clinical significance of CARDS toxin and pro-inflammatory cytokines in children with RMPP and to explore whether CARDS toxin can induce TNF-α expression. Methods Levels of CARDS toxin and cytokines in BALF from control and children with MPP were determined by real-time PCR and ELISA, respectively. A receiver-operating characteristic (ROC) analysis was performed to assess the diagnostic values of CARDS toxin, TNF-α, and IL-6 in RMPP. The recombinant CARDS toxin was constructed and prepared at different concentrations for stimulation of RAW264.7 cells. After co-culture with CARDS toxin, cytokines were detected by ELISA and the mRNA levels were measured by real-time PCR. Effects of CARDS toxin and TNF-α on inflammatory cell infiltration and mucus secretion in mouse lungs were also evaluated. Results Levels of CARDS toxin, TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF) were significantly higher in RMPP cases compared with NRMPP cases. Furthermore, TNF-α had better diagnostic ability for differentiation of RMPP with AUC of 0.824 and Youden index of 0.692 compared with CARDS toxin and IL-6. Moreover, CARDS toxin was positively correlated with TNF-α level in MPP cases. In vitro assay revealed that CARDS toxin induced RAW264.7 macrophages to secrete TNF-α. Further in vivo assay showed that TNF-α deletion partially abrogated the CARDS toxin-mediated induction of inflammatory cell infiltration and mucus secretion in mouse lungs. Conclusions The high co-expression of TNF-α and CARDS toxin in BALF is a good diagnostic biomarker for differentiating children with RMPP and NRMPP.

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

Cited by 27 publications

References 48 publications

Cytokine signatures associate with disease severity in children with Mycoplasma pneumoniae pneumonia

Cytokine signatures associate with disease severity in children with Mycoplasma pneumoniae pneumonia

Identification of Novel Genes and Biological Pathways That Overlap in Infectious and Nonallergic Diseases of the Upper and Lower Airways Using Network Analyses

High co-expression of TNF-α and CARDS toxin is a good predictor for refractory Mycoplasma pneumoniae pneumonia

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