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

Abstract

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.

The correlation between vitamin a status and refractory Mycoplasma Pneumoniae pneumonia (RMPP) incidence in children

“…Besides, there were trends for correlations with ferritin and TNF-α, which agreed with other' studies [43,44]. In the linear correlation test, we found a significantly negative correlation between IL-6 and vitamin A. M. pneumoniae infections are closely related to stimulation of macrophages via toll-like receptors that release immunomodulatory and inflammatory cytokines and chemokines [33].…”

Investigation of The Relationship Between CARDS TX and The HMGB1-TLRs-MyD88 Signaling Pathway in MPP

“…HMGB1 mRNA expression was also positively correlated with TLR2, MyD88, and CD14 mRNA expression (r = 0.639, 0.478, and 0.711, respectively; all P < 0.05, Table 5). related to the severity of MPP [4,11] . We studied children with the diagnosis of MPP who were examined by bronchoscopy and bronchoalveolar lavage.…”

“…TNF-α can activate production of secondary in ammatory mediators, such as IL-1β, which in turn promotes signal transmission of T cells to initiate the in ammatory response. Studies have shown that MP and CARDS TX stimulate production of pro-in ammatory cytokines, such as TNF-α and IL-1β [11,12] . TNF-α and IL-1β can also stimulate mononuclear macrophages to actively secrete HMGB1 to the extracellular environment to play a proin ammatory role [13] .…”

Clinical features of severe mycoplasma pneumoniae pneumonia with pulmonary complications in childhood: a retrospective study.

“…High-load MP could cause overwhelming immune response by direct and indirect damage to the host, causing the release of various enzymes, complements and biologically active substances to increase pleural capillary permeability resulting in formation of pleural effusion. In vitro and in vivo studies [18,19]have found that MP could causes extensive damage to airway and alveolar epithelial cells by pathogenic factor MPN 372, and MPN372 was capable of stimulating tumor necrosis factor-alpha production by macrophages [20], which might be involved in lung parenchymal necrosis. The formation of atelectasis is courses of lung collapse caused by airway obstruction,and MPP-associated atelectasis was resulted from mucus plug formation in local airway [5], indicating the inflammation of forming mucus plug might be mild compared with that contributing pleural effusion and lung necrosis.…”