The Immunopathologic Effects of Mycoplasma pneumoniae and Community-acquired Respiratory Distress Syndrome Toxin. A Primate Model.

Mycoplasma pneumoniae infection has been linked to poor asthma outcomes. M. pneumoniae produces an ADP-ribosylating and vacuolating toxin called community-acquired respiratory distress syndrome (CARDS) toxin that has a major role in inflammation and airway dysfunction. The objective was to evaluate the immunopathological effects in primates exposed to M. pneumoniae or CARDS toxin. A total of 13 baboons were exposed to M. pneumoniae or CARDS toxin. At Days 7 and 14, BAL fluid was collected and analyzed for cell count, percent of each type of cell, CARDS toxin by PCR, CARDS toxin by antigen capture, eosinophilic cationic protein, and cytokine profiles. Serum IgM, IgG, and IgE responses to CARDS toxin were measured. All animals had a necropsy for analysis of the histopathological changes on lungs. No animal developed signs of infection. The serological responses to CARDS toxin were variable. At Day 14, four of seven animals exposed to M. pneumoniae and all four animals exposed to CARDS toxin developed histological "asthma-like" changes. T cell intracellular cytokine analysis revealed an increasing ratio of IL-4/IFN-γ over time. Both M. pneumoniae and CARDS toxin exposure resulted in similar histopathological pulmonary changes, suggesting that CARDS toxin plays a major role in the inflammatory response.

Investigation of the relationship between community-acquired respiratory distress syndrome toxin and the high-mobility group box protein 1-toll-like receptors-myeloid differentiation factor 88 signaling pathway in Mycoplasma pneumoniae pneumonia.

BACKGROUND: In recent years, reports of refractory Mycoplasma pneumoniae pneumonia (RMPP) have gradually increased, including reports on how these conditions threaten the lives of children. However, the specific mechanism of Mycoplasma pneumoniae pneumonia (MPP) remains unclear. This study aimed to investigate the relationship between community-acquired respiratory distress syndrome toxin (CARDS TX) and High-mobility group box protein 1-Toll-like receptors-Myeloid differentiation factor 88 (HMGB1-TLRs-MyD88) in MPP and to examine the immune pathogenesis of Mycoplasma pneumoniae infection. METHODS: Children who were diagnosed with MPP and examined by bronchoscopy were included in the MPP group. Additionally, children who underwent bronchoscopy because of bronchial foreign bodies in the same period were included in the control group. Gene expression of CARDS TX, HMGB1, Toll-like receptor 2 (TLR2), Toll-like receptor 4 (TLR4), MyD88, and cluster of differentiation 14 (CD14) in bronchoalveolar lavage fluid (BALF) were detected using real-time reverse transcription-polymerase chain reaction. Correlations between CARDS TX and HMGB1-TLRs-MyD88 were analyzed. RESULTS: CARDS TX, HMGB1, TLR2, MyD88, and CD14 mRNA expression in BALF in the MPP group was significantly higher than that in the control group (all P < 0.05). CARDS TX mRNA expression was positively correlated with HMGB1, TLR2, MyD88, and CD14 mRNA expression (all P < 0.05). Furthermore, HMGB1 mRNA expression was positively correlated with TLR2, MyD88, and CD14 mRNA expression (all P < 0.05). CONCLUSIONS: CARDS TX may participate in the immune pathogenesis of MPP through the HMGB1-TLRs/CD14-MyD88 pathway.

Community-Acquired Respiratory Distress Syndrome Toxin: Unique Exotoxin for M. pneumoniae.

Mycoplasma pneumoniae infection often causes respiratory diseases in humans, particularly in children and adults with atypical pneumonia and community-acquired pneumonia (CAP), and is often exacerbated by co-infection with other lung diseases, such as asthma, bronchitis, and chronic obstructive pulmonary disorder. Community-acquired respiratory distress syndrome toxin (CARDS TX) is the only exotoxin produced by M. pneumoniae and has been extensively studied for its ADP-ribosyltransferase (ADPRT) activity and cellular vacuolization properties. Additionally, CARDS TX induces inflammatory responses, resulting in cell swelling, nuclear lysis, mucus proliferation, and cell vacuolization. CARDS TX enters host cells by binding to the host receptor and is then reverse transported to the endoplasmic reticulum to exert its pathogenic effects. In this review, we focus on the structural characteristics, functional activity, distribution and receptors, mechanism of cell entry, and inflammatory response of CARDS TX was examined. Overall, the findings of this review provide a theoretical basis for further investigation of the mechanism of M. pneumoniae infection and the development of clinical diagnosis and vaccines.

Research progress on community-acquired respiratory distress syndrome toxin / 临床儿科杂志

The Community-Acquired Respiratory Distress Syndrome toxin (CARDS TX) is one of the most important toxins produced by the Mycoplasma pneumoniae.The synthesis,distribution and bioactivity of this toxin have been gradually studied.It has been shown that CARDS TX has impact on the inflammation induced by Mycoplasma pneumoniae infection,and poorly controlled asthma. With further study on the pathomechanism of the CARDS TX, it would become a new key in arriving early or confirmed diagnosis and treatment about Mycoplasmal pneumonia.