Establishment of a rapid detection method for Mycoplasma pneumoniae based on RPA-CRISPR-Cas12a technology.

Mycoplasma pneumoniae can cause respiratory infections and pneumonia, posing a serious threat to the health of children and adolescents. Early diagnosis of Mycoplasma pneumoniae infection is crucial for clinical treatment. Currently, diagnostic methods for Mycoplasma pneumoniae infection include pathogen detection, molecular biology techniques, and bacterial culture, all of which have certain limitations. Here, we developed a rapid, simple, and accurate detection method for Mycoplasma pneumoniae that does not rely on large equipment or complex operations. This technology combines the CRISPR-Cas12a system with recombinase polymerase amplification (RPA), allowing the detection results to be observed through fluorescence curves and immunochromatographic lateral flow strips.It has been validated that RPA-CRISPR/Cas12a fluorescence analysis and RPA-CRISPR/Cas12-immunochromatographic exhibit no cross-reactivity with other common pathogens, and The established detection limit was ascertained to be as low as 102 copies/µL.Additionally, 49 clinical samples were tested and compared with fluorescence quantitative polymerase chain reaction, demonstrating a sensitivity and specificity of 100%. This platform exhibits promising clinical performance and holds significant potential for clinical application, particularly in settings with limited resources, such as clinical care points or resource-constrained areas.

New-generation tetracyclines for severe macrolide-resistant Mycoplasma pneumoniae pneumonia in children: a retrospective analysis.

BACKGROUND: Macrolide-resistant Mycoplasma pneumoniae (MRMP) strains are increasingly prevalent, leading to a rise in severe Mycoplasma pneumoniae pneumonia incidence annually, which poses a significant threat to children's health. This study aimed to compare the effectiveness and safety of oral minocycline and doxycycline for the treatment of severe MRMP pneumonia in children. METHODS: This retrospective analysis included children treated for severe MRMP pneumonia at the Pediatric Department of Tongji Hospital, Shanghai, China, between September 2023 and January 2024 using minocycline and doxycycline. The patients were divided into four groups according to treatment: oral doxycycline alone (DOX group), oral minocycline alone (MIN group), oral doxycycline with intravenous glucocorticoids (DOXG group), and oral minocycline with intravenous glucocorticoids (MING group). Student's t-test, Mann-Whitney U test, and χ2 or Fisher's exact tests were used for group comparisons. RESULTS: A total of 165 patients were included in this study: 84 received minocycline, and 81 received doxycycline. The DOX group had higher fever resolution rates within 24, 48, and 72 h compared to the MIN group (63.2% vs. 31.8%, 79.0% vs. 63.6%, and 100% vs. 90.9%, respectively; all p < 0.05). The DOXG group showed higher fever resolution rates within 24 and 48 h than the MING group (92.3% vs. 83.4%, 100% vs. 92.7%, all p > 0.05). There were no statistically significant differences in time to imaging improvement, cough improvement, and disappearance of wet rales between groups, regardless of glucocorticoid combination. The longer the duration of fever prior to tetracycline therapy, the greater the likelihood of hypoxemia (p = 0.039) and a greater than two-fold elevation in the D-dimer level (p = 0.004).Univariate binary logistic regression model analysis revealed that CRP and erythrocyte sedimentation rate at disease onset were associated with defervescence within 24 h after treatment with tetracyclines alone (p = 0.020, p = 0.027), with erythrocyte sedimentation rate also influencing defervescence within 48 h (p = 0.022). CONCLUSION: Doxycycline treatment resulted in a higher rate of defervescence than minocycline. Prompt treatment reduced the probability of pleural effusion, hypoxemia, pulmonary atelectasis, and D-dimer levels > 2 times the reference value.

Comparative observation between Roxithromycin and Azithromycin sequential therapy in the treatment of Mycoplasma pneumoniae Pneumonia in Children.

Objective: To investigate the clinical efficacy of roxithromycin combined with azithromycin sequential therapy in the treatment of mycoplasma pneumoniae pneumonia in children. Methods: A retrospective study was conducted on 100 patients with mycoplasma pneumoniae pneumonia admitted to The First Affiliated Hospital of Yangtze University from January 2020 to December 2022. All patients were divided into the observation group (roxithromycin combined with azithromycin sequential therapy) and the control group (azithromycin sequential therapy), with 50 cases in each group. The clinical efficacy, improvement time of clinical symptoms/signs, inflammation indexes, oxidative stress indexes and immune function levels of the two groups were compared. Moreover, the improvement of lung function indexes and the adverse reactions were observed. Results: The overall response rate of the observation group was 96.00%, which was higher than the control group (84.00%) (p<0.05). The time of clinical symptoms/signs in the observation group were significantly lower than those in the control group(p<0.05). After treatment, significant improvements were seen in the levels of CRP, TNF-ɑ, IL-6, GSH-Px, SOD, MDA, CD3+, CD4+, CD4+/CD8+, IgM, IgG , IgA, FEV1, FEV1%, FVC and FEV1/FVC of the two groups compared with those before treatment (p<0.05), and the improvement in the observation group was more obvious than that in the control group(p<0.05). The overall incidence of adverse reactions in the observation group was 6.00%, which was slightly lower than that in the control group (8.00%) (c²=0.154, P=0.695). Conclusion: Roxithromycin combined with azithromycin sequential therapy is a safe regimen for the treatment of mycoplasma pneumoniae pneumonia in children.

Predicting the severity of mycoplasma pneumoniae pneumonia in pediatric and adult patients: a multicenter study.

The purpose of this study is to develop a nomogram model for early prediction of the severe mycoplasma pneumoniae pneumonia (SMPP) in Pediatric and Adult Patients. A retrospective analysis was conducted on patients with MPP, classifying them into SMPP and non-severe MPP (NSMPP) groups. A total of 550 patients (NSMPP 374 and SMPP 176) were enrolled in the study and allocated to training, validation cohorts. 278 patients (NSMPP 224 and SMPP 54) were retrospectively collected from two institutions and allocated to testing cohort. The risk factors for SMPP were identified using univariate analysis. For radiomic feature selection, Spearman's correlation and the least absolute shrinkage and selection operator (LASSO) were utilized. Logistic regression was used to build different models, including clinical, imaging, radiomics, and integrated models (combining clinical, imaging, and radiomics features selected). The model's discrimination was evaluated using a receiver operating characteristic curve, its calibration with a calibration curve, and the results were visualized using the Hosmer-Lemeshow goodness-of-fit test. Thirteen clinical features and fourteen imaging features were selected for constructing the clinical and imaging models. Simultaneously, a set of twenty-five radiomics features were utilized to build the radiomics model. The integrated model demonstrated good calibration and discrimination in the training cohorts (AUC, 0.922; 95% CI: 0.900, 0.942), validation cohorts (AUC, 0.879; 95% CI: 0.806, 0.920), and testing cohorts (AUC, 0.877; 95% CI: 0.836, 0.916). The discriminatory and predictive efficacy of the clinical model in testing cohorts increased further after clinical and radiological features were incorporated (AUC, 0.849 vs. 0.922, P = 0.002). The model demonstrated exemplary predictive efficacy for SMPP by leveraging a comprehensive set of inputs, encompassing clinical data, quantitative and qualitative radiological features, along with radiomics features. The integration of these three aspects in the predictive model further enhanced the performance of the clinical model, indicating the potential for extensive clinical applications.

Mycoplasma bovis-associated verminous pneumonia in alpine chamois (Rupicapra rupicapra).

Pneumonia is a common disease affecting Alpine chamois. However, little is known concerning the etiological agents involved. We investigated whether Mycoplasma spp. infection occurs in Alpine chamois and describe the microscopic lesions associated with Mycoplasma-associated bronchopneumonia in this species. Lung tissues obtained from 45 chamois with gross evidence of pneumonia were analysed. The histological lesions and the presence of lungworms within the lungs were evaluated blindly. The presence of Mycoplasma spp. was assessed by immunohistochemistry (Mycoplasma bovis and Mycoplasma mycoides subsp. mycoides) and by end-point PCR. M. bovis was detected by immunohistochemistry and confirmed by PCR and sequencing in 6/45 (13%) cases, while all lungs were negative for M. mycoides subsp. mycoides. A significant association was found between the detection of M. bovis and the presence of severe lungworms infection in the examined lungs. We report for the first time M. bovis as a bacteria associated with verminous pneumonia in chamois.

Molecular mechanism of Dang-Shen-Yu-Xing decoction against Mycoplasma bovis pneumonia based on network pharmacology, molecular docking, molecular dynamics simulations and experimental verification.

Mycoplasma bovis pneumonia is a highly contagious respiratory infection caused by Mycoplasma bovis. It is particularly prevalent in calves, posing a significant threat to animal health and leading to substantial economic losses. Dang-Shen-Yu-Xing decoction is often used to treat this condition in veterinary clinics. It exhibits robust anti-inflammatory effects and can alleviate pulmonary fibrosis. However, its mechanism of action remains unclear. Therefore, this study aimed to preliminarily explore the molecular mechanism of Dang-Shen-Yu-Xing decoction for treating mycoplasma pneumonia in calves through a combination of network pharmacology, molecular docking, molecular dynamics simulation methods, and experimental validation. The active components and related targets of Dang-Shen-Yu-Xing decoction were extracted from several public databases. Additionally, complex interactions between drugs and targets were explored through network topology, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Subsequently, the binding affinity of drug to disease-related targets was verified through molecular docking and molecular dynamics simulation. Finally, the pharmacodynamics were verified via animal experiments. The primary network topology analysis revealed two core targets and 10 key active components of Dang-Shen-Yu-Xing decoction against Mycoplasma bovis pneumonia. Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that the mechanism of Dang-Shen-Yu-Xing decoction for treating mycoplasma bovis pneumonia involved multiple signaling pathways, with the main pathways including PI3K-Akt and IL17 signaling pathways. Moreover, molecular docking predicted the binding affinity and conformation of the core targets of Dang-Shen-Yu-Xing decoction, IL6, and IL10, with the associated main active ingredients. The results showed a strong binding of the active ingredients to the hub target. Further, molecular docking dynamics simulation revealed three key active components of IL10 induced by Dang-Shen-Yu-Xing decoction against Mycoplasma bovis pneumonia. Finally, animal experiments confirmed Dang-Shen-Yu-Xing decoction pharmacodynamics, suggesting that it holds potential as an alternative therapy for treating mycoplasma bovis pneumonia.

Atypical Stevens-Johnson Syndrome in a Patient With Mycoplasma pneumoniae Infection: A Case Report.

Stevens-Johnson syndrome (SJS) is a serious condition involving the skin and mucous membranes and is characterized by extensive necrosis and detachment of the epidermis. We present a case report of atypical SJS occurring as a complication of Mycoplasma pneumoniae infection in a young adult patient. This case report aims to add to the limited body of literature that exists on the topic and remind clinicians of the possible diagnosis of atypical SJS in the setting of mucosal rash associated with M. pneumoniae infection.

A comprehensive review of Mycoplasma pneumoniae infection in chronic lung diseases: recent advances in understanding asthma, COPD, and bronchiectasis.

This review summarizes the research progress over the past 30 years on the relationship between Mycoplasma pneumoniae infection and chronic respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and bronchiectasis. Mycoplasma pneumoniae is a common cause of community-acquired pneumonia, particularly in children and young adults. Key findings from recent studies indicate that M. pneumoniae infection is associated with a higher risk of asthma exacerbations and may contribute to the development of bronchiectasis in susceptible individuals. Additionally, emerging evidence suggests that M. pneumoniae-induced immune dysregulation plays a crucial role in the pathogenesis of chronic lung diseases. This review aims to summarize the current understanding of the potential links between M. pneumoniae pneumonia and various chronic respiratory conditions, including asthma, chronic obstructive pulmonary disease (COPD), and bronchiectasis. We discuss the epidemiological data, pathogenic mechanisms, clinical manifestations, and long-term consequences of M. pneumoniae-related respiratory illnesses. Additionally, we highlight the challenges in diagnosis and treatment, as well as future research directions in this field.

Protection against Mycoplasma hyorhinis infection in commercial pigs via immunization with inactivated vaccines prepared with homologous or heterologous strains.

Mycoplasma hyorhinis is a highly prevalent pathogen in pig farms worldwide, causing polyserositis and polyarthritis, resulting in great economic losses. Previous genotyping and pathogenic studies have revealed significant genetic and antigenic diversity among M. hyorhinis strains. While there are reports on M. hyorhinis vaccine development, the cross-protection between different M. hyorhinis strains has not been clarified. In this study, two M. hyorhinis strains (HEF-16 and JS-54), belonging to different sequence types, were inactivated to produce vaccines. Pigs were vaccinated respectively and subsequently infected with strain HEF-16. The protection against challenge with homologous or heterologous strains was determined and compared. Both vaccinated groups of pigs exhibited a high antibody titer two weeks after the first vaccination, and significant decreases in pathogen load in joints, along with an increase in average daily weight gain compared to the challenged group after M. hyorhinis challenge. Pigs immunized with the HEF-16-derived vaccine showed a significant reduction in joint swelling and lameness, similar to pigs immunized with the JS-54-derived vaccine. At necropsy, animals in the challenged group exhibited moderate-to-severe polyserositis and arthritis, whereas pathological changes were greatly reduced in animals from the vaccinated groups. No significant differences were observed in clinical symptoms nor pathological damages between the two vaccinated groups. Overall, our study demonstrates the effective protection of the inactivated M. hyorhinis vaccines against challenges with homologous or heterologous strains in commercial pigs. This indicates a promising clinical application prospect for inactivated bacterin vaccines in preventing M. hyorhinis-related diseases in pig farms.

An automated commercial open access assay for detection of Mycoplasma genitalium macrolide resistance.

Azithromycin, a macrolide antibioticum, is the first-line treatment for Mycoplasma genitalium (MG), but resistant MG is an increasing problem. Macrolide resistance-mediated mutations (MRM) has been linked to point mutations in region V of the MG 23S rRNA gene. We have evaluated an open access analyzer (Panther Fusion, Hologic Inc) for detectability of MRM (mutations A2071G and A2072G) and MG wild type (WT) in clinical samples. Also, the agreement of the Panther Fusion assay results with a corresponding established In-house MRM-WT PCR (ABI 7500) was calculated. Left over material from 55 clinical samples positive for MG by the Aptima test (Hologic) based on transcription-mediated amplification (TMA), collected from January to February 2023 in Region Skåne, Sweden, was analyzed. Specific amplification curves were generated for positive controls of MG mutations (A2071G and A2072G) and WT by the Panther Fusion assay. The limit of detection (LOD) was 5.3 copies/mL for WT, 8.1 copies/mL for mutation A2071G, and 81 copies/mL for mutation A2072G. The overall concordance was 91% between the Panther Fusion and the In-house PCR (Kappa 0.621, 95% CI; 0.327-0.914) for detection of WT or MRM in MG-positive clinical samples. The Panther Fusion detected MRM in 20% (11/55) and WT in 62% (34/55) of the samples. The corresponding In-house PCR results were 25% (14/55) and 65% (36/55). In summary, the Panther Fusion assay demonstrated detection of low copy number of MRM and WT of MG. Among clinical samples substantial agreement between the Panther Fusion and In-house PCR results was observed. Integrating MG-analysis (TMA) and MRM-WT assay on the Panther platform could make MRM testing more readily available. However, the Panther Fusion had a lower success rate (82% vs 90%) for macrolide susceptibility testing, hence testing with a complementary method should be considered for samples where neither WT nor MRM MG are detectable.

The efficacy of azithromycin combined with seven types of Chinese medicine injections in the treatment of Mycoplasma pneumoniae pneumonia in children: a systematic review and Bayesian network meta-analysis.

Mycoplasma pneumoniae pneumonia (MPP) is the predominant community-acquired pneumonia (CAP) in children aged 5 years or older. In recent decades, the annual increase in drug resistance rates of macrolide antibiotics, particularly azithromycin (AZ), has led to complex clinical treatment strategies and substantial healthcare costs associated with MPP. Chinese medicine injections (CMIs), recognized as an effective supplementary therapy, are acknowledged by clinicians in China. It is necessary to explore the efficacy of azithromycin in combination with CMIs. Methods: Randomized controlled trials (RCTs) evaluating azithromycin in combination with seven types of CMIs for MPP in children were identified based on inclusion criteria and assessed using the revised Cochrane risk of bias tool (RoB 2.0). R 4.3.1 and STATA 15.0 were employed to generate ranking probabilities and perform network meta-analysis. Competing interventions were ranked using the surface under the cumulative ranking (SUCRA) probabilities. Results: A comprehensive analysis was performed on 155 RCTs involving 15,014 patients and 8 therapeutic strategies within this Bayesian network meta-analysis (BNMA). The results indicated that AZ combined with seven types of CMIs was more effective than azithromycin alone in overall outcomes. Notably, azithromycin combined with Chuanhuning injection (AZ + CHN) achieved the highest ranking in improving the clinical effectiveness rate (SUCRA, 80.89%); regarding secondary outcome measures, azithromycin combined with Yanhuning injection (AZ + YHN) had the highest probability of improving four different outcomes: disappearance time of cough (SUCRA, 80.01%), disappearance time of pulmonary rale (SUCRA, 87.77%), disappearance time of fever (SUCRA, 95.70%), and disappearance time of pulmonary shadows in X-ray (SUCRA, 97.34%); furthermore, azithromycin combined with Qingkailing injection (AZ + QKL) was more likely to reduce average hospitalization time (SUCRA, 94.60%). Conclusion: This study highlights the potential benefits of seven types of Chinese medicine injections as adjunctive therapy for Mycoplasma pneumoniae pneumonia in children. However, further support and validation of these findings are needed through high-quality randomized controlled trials with larger sample sizes and double-blind designs. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails/.

Computerized Decision Support Systems Informing Community-Acquired Pneumonia Surveillance, France, 2017-2023.

We show the value of real-time data generated by a computerized decision support system in primary care in strengthening pneumonia surveillance. The system showed a 66% (95% CI 64%-67%) increase in community-acquired pneumonia from 2018 to 2023 for the population of France, 1 month before a national alert was issued.

Mycoplasma pneumoniae regulates the expression of GP130 in lung epithelial cells through apoptosis and TLR4/ NF-κB pathway during infection.

In previous study, lower levels of serum GP130 were reported in children with MPP. GP130 is an important signal transducer, the down regulation of which may influence host immune responses. In this study, we aimed to analyze the regulatory mechanism of GP130 during MP infection. Firstly, the mRNA and protein levels of GP130 both decrease and then increase with increasing multiplicity of infection (MOI: 1 to 40) of MP. The lowest levels of GP130 were detected at MOI of 5. Then, heat treated MP but not trypsin treated MP or MP extracted proteins show regulatory effect to the expression of GP130. These indicate that the down regulation of GP130 is related to protein mediate adhesion process of MP. Gene expression analysis revealed that MP affected apoptosis and the TLR4 pathway in infected cells, and the mRNA level of IL-6 was correlated with that of GP130. Further, Z-VAD-FMK (pan-caspase inhibitor) can suppress the apoptosis induced by MP infection and restore GP130 at protein level. Further studies revealed that MP infection promoted TLR4 internalization but did not activate the NF-κB pathway. The levels of surface TLR4 showed correlation with the transcription of IL-6 and GP130. TAK242 (TLR4 inhibitor) and PS341 (proteasome inhibitor) can restore the decreased transcription of GP130, both of which were able to promote NF-κB pathway activation in MP-infected cells. These suggested that the regulation of TLR4/NF-κB pathway and induced apoptosis post MP infection are involved in the down-regulation of GP130 at transcription and protein levels, respectively.

Respiratory pathogen analysis in pediatric inpatients unraveled the infection pattern of Mycoplasma pneumoniae post the COVID-19 pandemic.

Background: To counteract the COVID-19 pandemic, nonpharmaceutical interventions (NPIs) were implemented globally, exerting a profound influence on a wide spectrum of infectious diseases, encompassing respiratory tract infections (RTIs). Subsequent to the easing of NPIs, China experienced a significant outbreak of Mycoplasma pneumoniae (MP). Methods: Over a decade from 2015 to 2024, our study scrutinized 12 common infectious diseases among pediatric children. Etiologically diagnostic data and clinical outcome metrics of children with RTIs, tested for 13 pathogens, were analyzed to evaluate changes during and after the pandemic compared to pre-pandemic periods, with a notable emphasis on age profile and coinfection patterns of MP. Results: Among 57,471 hospitalized children, 23,178 were diagnosed with infectious diseases. Under NPIs, most respiratory infections declined compared to pre-pandemic levels, rebounding by 69.64% in 2023. While the infection rate of common respiratory pathogens decreased, cases of respiratory syncytial virus increased during the period of extensive NPI implementation. In 2023, pediatric intensive care unit durations for these pathogens increased, suggesting greater severity of illness compared to 2019. MP exhibited the highest infection rate (31.38% average), with a notable outbreak post-pandemic due to severity increase in <3 year olds and rise among older children. NPIs reduced MP coinfections and mitigated their severity, while exerting a significant influence on bacterial coinfections with MP over the span of 5 years, in contrast to their impact on viral pathogens. Conclusion: NPIs effectively curb transmission of respiratory infections by most pathogens, resulting in increased average age of MP infections and altered patterns of coinfection post-pandemic.

The Clinical Significance of Pathogen Loads and Macrolide Resistance Levels for Macrolide-Resistant Mycoplasma pneumoniae Pneumonia in Children.

Objective: Mycoplasma pneumoniae (M. pneumoniae) pneumonia presses a serious threat on children's health. This study was aimed to investigate the clinical significance of pathogen loads and macrolide resistance levels for macrolide-resistant M. pneumoniae (MRMP)-induced pneumonia in children. Methods: Serum levels of inflammatory markers including lactic dehydrogenase (LDH), D-dimer, C-reactive protein (CRP) were tested. RT‒PCR was used for the detection of M. pneumoniae infection and the macrolide resistance levels. The patients were classified into high pathogen load and low pathogen load groups based on the Ct values of the p1 gene, and high macrolide resistance level and low macrolide resistance level groups based on the relative levels of macrolide resistance associated mutations to that of the p1 gene. The rates of alternative antibiotic use and hospitalization days were recorded, and the leukocyte counts were tested. Results: The rates of elevated inflammatory markers from high to low were LDH, CRP and D-dimer. The Ct values of the p1 gene ranged from 19 to 35, and patients with higher pathogen loads had greater rates of alternative antibiotic use; higher levels of LDH, D-dimer, CRP and neutrophil counts (NEUT); and longer hospitalization durations. The range of the macrolide resistance levels was 0.31-2.11, and the rates of alternative antibiotic use, NEUT, CRP and D-dimer levels were higher in patients with higher macrolide resistance levels. Conclusion: LDH was a more frequently elevated serum inflammatory marker than D-dimer and CRP, and the pathogen load and macrolide resistance levels possessed important clinical significance for MRMP-induced pneumonia in children.

Application of Protein Expression in Mycoplasma Study.

Mycoplasma is a kind of pathogenic microorganism, and its survival and replication need to be parasitic inside the host cell. Therefore, studies on the metabolic pathway, protein composition, and biological characteristics of Mycoplasma require the use of protein expression techniques. In this paper, the application of protein expression in Mycoplasma research was reviewed, including commonly used protein expression systems, optimization strategy of protein expression, protein omics analysis, and protein function research, and the future development direction has been prospected.

Lemierre Syndrome in the Setting of Bacteremia and Atypical Pneumonia: A Case Report.

Lemierre syndrome is an uncommon condition that typically presents with oropharyngeal infection and subsequent thrombophlebitis of the internal jugular veins. The syndrome is associated with septic emboli, frequently of the lungs, as well as Fusobacterium necrophorum bacteremia. Here, we report a case of Lemierre syndrome in the setting of an atypical pulmonary pathology. During the patient's clinical course, a peritonsillar abscess was identified, as well as associated septic emboli and superimposed Mycoplasma pneumoniae in the setting of F. necrophorum bacteremia. Prompt imaging and antibiotic treatment, in addition to an incision and drainage of the peritonsillar abscess, allowed for the patient to be medically optimized for discharge home with intravenous and oral antibiotics. Early recognition of this rare syndrome can help guide treatment and promote positive outcomes for patients affected by Lemierre syndrome.

Single-cell transcriptome atlas revealed bronchoalveolar immune features related to disease severity in pediatric Mycoplasma pneumoniae pneumonia.

The mechanisms underlying protective immunity in mild Mycoplasma pneumoniae pneumonia (MPP) and the pathogenesis of severe MPP, characterized by dysregulated immune responses, remain unclear. Here, we performed single-cell RNA sequencing (scRNA-seq) to profile bronchoalveolar lavage fluid (BALF) samples from 13 healthy donors and 24 hospitalized pediatric patients with MPP, covering both mild and severe cases. Severe MPP patients exhibited high levels of exhausted T cells and M1-like macrophages, with the exhaustion of T cells attributed to persistent type I interferon signaling and inadequate assistance from CD4+ T cells. Significant cell-cell interactions between exhausted T cells and programmed death-ligand 1+ (PD-L1+) macrophages were detected in severe patients, potentially mediated through inhibitor molecules (e.g., PD1) and their receptors (e.g., PD-L1), as well as human leukocyte antigen class I molecules and their receptors (e.g., KLRC1/D2), resulting in the dysfunction of anti-MP immune responses. Mild MPP patients were featured by an increased abundance of neutrophils, coupled with enhanced activation, contributing to protective immunity. Together, our study provides a detailed characterization of the BALF immune landscape in MPP patients, revealing distinct immune characteristics between mild and severe cases, which offers a valuable resource for understanding MPP immunopathogenesis and formulating effective therapeutic strategies.

Association of serum interleukin-17 level and Mycoplasma pneumoniae pneumonia in children: a systematic review and meta-analysis.

Background: Mycoplasma pneumoniae (M. pneumoniae) is a common pathogen of community-acquired pneumonia. Interleukin-17 (IL-17) plays a role in host defense and contributes to disease severity in infection. This present study aims to investigate the association between Mycoplasma pneumoniae pneumonia (MPP) and changes of IL-17 level in the serum of pediatric patients. Methods: The protocol has been registered in PROSPERO (CRD42023489451). A literature search was conducted in PubMed, EMBASE, Scopus, and Web of Science from inception to October 2023. A meta-analysis was performed to pool the mean difference (MD) with 95% confidence intervals (CIs) of IL-17 levels between patients and controls. Publication bias was assessed, and the risk of bias was evaluated using the Newcastle-Ottawa Scale (NOS). Results: Out of 207 records, 10 studies were included in the review and 9 studies were included in the meta-analysis. Of these, 7 studies compared IL-17 in general MPP patients with controls, 6 studies compared severe MPP patients with mild MPP patients. Serum IL-17 levels were significantly elevated in general MPP patients compared with control (MD =33.94 pg/mL, 95% CI: 24.66, 43.22 pg/mL, P=0.01, I2=99.07%; P=0.01). Subgroup analyses showed a difference in serum IL-17 levels treated by macrolide between patients and control (MD =83.96 pg/mL, 95% CI: 76.62, 91.29 pg/mL, P=0.01). In severe and mild MPP, the IL-17 levels were significantly increased (MD =19.08 pg/mL, 95% CI: 11.51, 26.65 pg/mL, P=0.01) and heterogeneity was appeared (I2=99.39%; P=0.01). For the risks of bias, two studies had a "high risk" in comparability domain, and the 7 studies were classified as "low risk" and "unclear risk". Conclusions: Our meta-analysis revealed that serum IL-17 levels are significantly elevated in pediatric with general and severe MPP. IL-17 might be a potential biomarker or therapeutic target for pneumonia caused by M. pneumoniae.