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Role of the Mycoplasma pneumoniae/Interleukin-8/Neutrophil Axis in the Pathogenesis of Pneumonia.

ABSTRACT: Neutrophil infiltration is the characteristic pathological feature of M. pneumoniae pneumonia (MPP). This study aimed to explore the associations among neutrophil activity, clinical presentation, and role of the M. pneumoniae/interleukin-8 (IL-8)/neutrophil axis in the pathogenesis of MPP. A total of 42 patients with MPP were prospectively enrolled in the study. Neutrophil activity, including matrix metalloproteinase-9 (MMP-9), myeloperoxidase (MPO), and neutrophil elastase (NE), were measured. Clinical information was collected for all patients and control group. In vitro, IL-8 production was measured at different time points after M. pneumoniae infection of bronchial epithelial cells, and neutrophil activity was analyzed after IL-8 stimulation. The percentage of neutrophil in the bronchoalveolar lavage fluid was higher in the group of patients with high levels of M. pneumoniae DNA than in those with low levels of M. pneumoniae DNA (P < 0.05). IL-8, MMP-9, and NE in patients with MPP significantly increased compared with controls and decreased after treatment (P < 0.05). MPO and MMP-9 were associated with duration of fever (r = 0.332, P < 0.05) and length of stay (r = 0.342, P < 0.05), respectively. In vitro, M. pneumoniae induced IL-8 production by bronchial epithelial cells in a time dependent manner. MPO, MMP-9 and NE production by neutrophils significantly increased compared with medium controls after IL-8 stimulation. In summary, the M. pneumoniae/IL-8/neutrophil axis likely plays a vital role in the pathogenesis of MPP.

SUBMITTER: Chen Z

PROVIDER: S-EPMC4708980 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Decreased Interleukin-10 Responses in Children with Severe Mycoplasma pneumoniae Pneumonia.

Project description:Several cytokines may play roles in the immunological pathogenesis of mycoplasmal pneumonia caused by Mycoplasma pneumoniae. In this study, we investigated serum cytokine profiles in children with mycoplasmal pneumonia. The serum levels of interleukin (IL)-8, IL-10, and IL-18 were examined using ELISA kits in 34 patients with M. pneumoniae infection (Group 1, 11 with severe mycoplasmal pneumonia; Group 2, 13 with mild mycoplasmal pneumonia; Group 3, 10 with asthma) and 32 age-matched, non-infected controls. The serum levels of IL-8, IL-10, and IL-18 increased significantly in patients with mycoplasmal pneumonia compared with those in controls (P<0.01). The serum levels of IL-10 decreased significantly in Group 1 compared with those in Group 2 (P<0.01). The serum levels of IL-18 increased significantly in Group 1 compared with those in Group 2 (P<0.01). The serum levels of IL-10 and IL-18 decreased significantly in 10 M. pneumoniae-infected patients with asthma compared with those in 24 M. pneumoniae-infected patients without asthma (P<0.01). We examined the level of interleukins (IL-8, IL-10 and IL-18) after the patients started therapy. The data showed that IL-18 were lower after therapy (P<0.01). Collectively, our data suggested that these cytokines may be involved in the pathogenesis of mycoplasmal pneumonia.

| S-EPMC4708986 | biostudies-literature

Interleukin 17A as a good predictor of the severity of Mycoplasma pneumoniae pneumonia in children.

Project description:Early distinction between severe Mycoplasma pneumoniae pneumonia (MPP) and mild MPP is still difficult. The aim of this study was to analyze cytokines in bronchoalveolar lavage fluid (BALF) and explore predicting factors of severe MPP in children. Retrospective analysis was performed on 150 children with MPP or bronchial foreign body (FB) admitted in our hospital. The mRNA levels of IL17A were found significantly lower in severe MPP group comparing with mild MPP group or FB group. However, no significant difference was found in the levels of IL4, IL10 or interferon beta1 (IFN?1) between the two groups. Receiver operator characteristic (ROC) curve analysis showed that IL17A can be used to distinguish severe MPP from mild MPP. These results were confirmed in a validation cohort including 40 MPP children from another hospital. IL17A levels were correlated with some clinical characters, such as refractoriness and pleural effusion. Lower IL17A levels were more likely to be found in refractory MPP children or in MPP children with pleural effusion. Moreover, the protein levels of IL17A in BALF were also found greatly decreased in children with severe MPP. Thus, decreased IL17A levels in BALF may be a valuable biomarker to identify severe MPP in children.

| S-EPMC5636901 | biostudies-other

Ribosomal RNA‑depleted RNA sequencing reveals the pathogenesis of refractory <i>Mycoplasma pneumoniae</i> pneumonia in children.

Project description:Pneumonia caused by Mycoplasma pneumoniae (M. pneumoniae) is a major cause of community‑acquired pneumonia in children. In some cases, M. pneumoniae pneumonia (MPP) can develop into refractory MPP (RMPP), which shows no clinical or radiological response to macrolides, and can progress to severe and complicated pneumonia. However, the pathogenesis of RMPP remains poorly understood. The present study aimed to identify target genes that could be used as biomarkers for the clinical diagnosis of early‑stage RMPP through high‑throughput sequencing technology. The differences in long non‑coding (lnc)RNAs, mRNAs and circular (circ)RNAs were examined between whole‑blood samples from two patients with non‑refractory MPP (NRMPP), two patients with RMPP and three healthy children using ribosomal (r)RNA‑depleted RNA‑sequencing techniques and an integrated mRNA/circRNA analysis. A total of 17 lncRNAs (four upregulated and 13 downregulated), 18 mRNAs (six upregulated and 12 downregulated) and 24 circRNAs (12 upregulated and 12 downregulated) were the most significantly differentially expressed (P<0.05) between the NRMPP and RMPP groups. Upon functional analysis, the significantly differentially expressed genes encoded by the targeting mRNAs (prostaglandin‑endoperoxide synthase 2, IL‑8 and fos‑like antigen 1) were screened and identified to be enriched in the 'IL‑17 signaling pathway'. Furthermore, the key circRNAs in the NRMPP and RMPP comparative groups were primarily enriched in 'herpes simplex virus 1 infection', 'viral carcinogenesis' and 'RNA transport'. In the present study, a comprehensive analysis of the differences between the NRMPP and RMPP cases was performed based on rRNA‑depleted RNA‑sequencing techniques, and the selected genes and circRNAs may be closely associated with the complex pathogenesis of RMPP.

| S-EPMC8436218 | biostudies-literature

Role of Probiotics in Mycoplasma pneumoniae Pneumonia in Children: A Short-Term Pilot Project.

Project description:Mycoplasma pneumoniae is one of the most common pathogens causing community-acquired pneumonia in children. Mycoplasma pneumoniae pneumonia (MPP) can be successfully treated with azithromycin; however, antibiotic-associated diarrhea (AAD) is a common adverse effect. Increasing evidence suggests that some probiotics may prevent the development of AAD. The present study determined the effects of probiotics (live Clostridium butyricum plus Bifidobacterium infantis) on the prevention and treatment of AAD in children with MPP when co-administered with intravenous azithromycin. Fifty-five children with MPP were enrolled and received azithromycin (10 mg/kg/day; once daily for 7 days) combined with probiotics (starting on the third day of azithromycin treatment; 1,500 mg three times daily); 50 healthy children served as controls. At the end of the trial, the incidence of AAD, fecal microbiota, intestinal mucosal barriers, and systemic inflammation were analyzed using recommended systems biology techniques. No cases of AAD or other adverse events occurred in children with MPP after co-administration of probiotics with azithromycin. A live C. butyricum plus B. infantis preparation partly reconstructed the gut microbiota, especially restoration of bacterial diversity. The indicators of intestinal mucosal barrier function, such as D-lactate, endotoxin, and diamine oxidase, were significantly improved and the systemic inflammation (interleukin 10) was attenuated after probiotic therapy. The present study indicated that co-administration of probiotics with azithromycin is a promising therapy for MPP treatment which could prevent and treat AAD effectively.

| S-EPMC6334620 | biostudies-literature

Mycoplasma pneumoniae Among Children Hospitalized With Community-acquired Pneumonia.

Project description:BackgroundThe epidemiology of Mycoplasma pneumoniae (Mp) among US children (<18 years) hospitalized with community-acquired pneumonia (CAP) is poorly understood.MethodsIn the Etiology of Pneumonia in the Community study, we prospectively enrolled 2254 children hospitalized with radiographically confirmed pneumonia from January 2010-June 2012 and tested nasopharyngeal/oropharyngeal swabs for Mp using real-time polymerase chain reaction (PCR). Clinical and epidemiological features of Mp PCR-positive and -negative children were compared using logistic regression. Macrolide susceptibility was assessed by genotyping isolates.ResultsOne hundred and eighty two (8%) children were Mp PCR-positive (median age, 7 years); 12% required intensive care and 26% had pleural effusion. No in-hospital deaths occurred. Macrolide resistance was found in 4% (6/169) isolates. Of 178 (98%) Mp PCR-positive children tested for copathogens, 50 (28%) had ≥1 copathogen detected. Variables significantly associated with higher odds of Mp detection included age (10-17 years: adjusted odds ratio [aOR], 10.7 [95% confidence interval {CI}, 5.4-21.1] and 5-9 years: aOR, 6.4 [95% CI, 3.4-12.1] vs 2-4 years), outpatient antibiotics ≤5 days preadmission (aOR, 2.3 [95% CI, 1.5-3.5]), and copathogen detection (aOR, 2.1 [95% CI, 1.3-3.3]). Clinical characteristics were non-specific.ConclusionsUsually considered as a mild respiratory infection, Mp was the most commonly detected bacteria among children aged ≥5 years hospitalized with CAP, one-quarter of whom had codetections. Although associated with clinically nonspecific symptoms, there was a need for intensive care in some cases. Mycoplasma pneumoniae should be included in the differential diagnosis for school-aged children hospitalized with CAP.

| S-EPMC6552676 | biostudies-literature

Value of serum Mycoplasma pneumoniae immunoglobulin in the diagnosis of mycoplasma-related pneumonia in newborns.

Project description:Mycoplasma pneumoniae (M. pneumoniae) is an important pathogen of neonatal acquired pneumonia in newborns. Rapid and accurate diagnosis of M. pneumoniae infection is critical because timely antibiotic therapy can reduce drug overuse and prevent the development of bacterial resistance. Anti-M. pneumoniae immunoglobulin M (IgM) is an indicator of early infection that can persist for several months. Studies have shown that anti-M. pneumoniae IgA in adults is a reliable indicator of early M. pneumoniae infection. The aim of this study was to assess the association between M. pneumoniae IgA, IgM and IgG in mycoplasma-associated pneumonia. We recruited 80 newborns with pneumonia with potency of serum M. pneumoniae IgM positive or two sera anti-M. pneumoniae IgG increased by 4-fold. The potency of serum M. pneumoniae IgA, IgM and IgG were detected. The initial positive rates of IgM and IgA in M. pneumoniae were 63.6 and 33.8%, respectively, after infection. The positive rate of IgM and IgA in M. pneumoniae increased to 97.5 and 56.3%, respectively, at one week after infection. Compared with anti-M. pneumoniae IgA, anti-M. pneumoniae IgM has higher sensitivity in the diagnosis of neonatal mycoplasma-associated pneumonia. Detection of two sera can more effectively improve the diagnostic accuracy.

| S-EPMC5525573 | biostudies-other

Macrolide-Resistant Mycoplasma pneumoniae Infections in Pediatric Community-Acquired Pneumonia.

Project description:A high prevalence rate of macrolide-resistant Mycoplasma pneumoniae (MRMP) has been reported in Asia. We performed a systematic review and meta-analysis to investigate the effect of macrolide resistance on the manifestations and clinical judgment during M. pneumoniae infections. We found no difference in clinical severity between MRMP and macrolide-sensitive Mycoplasma pneumoniae (MSMP) infections. However, in the pooled data, patients infected with MRMP had a longer febrile period (1.71 days), length of hospital stay (1.61 day), antibiotic drug courses (2.93 days), and defervescence time after macrolide treatment (2.04 days) compared with patients infected with MSMP. The risk of fever lasting for >48 hours after macrolide treatment was also significantly increased (OR 21.24), and an increased proportion of patients was changed to second-line treatment (OR 4.42). Our findings indicate diagnostic and therapeutic challenges after the emergence of MRMP. More precise diagnostic tools and clearly defined treatment should be appraised in the future.

| S-EPMC7323531 | biostudies-literature

Double-Edged Role of Interleukin 17A in Streptococcus pneumoniae Pathogenesis During Influenza Virus Coinfection.

Project description:BACKGROUND:We sought to determine the role of host interleukin 17A (IL-17A) response against colonizing Streptococcus pneumoniae, and its transition to a pathogen during coinfection with an influenza virus, influenza A H1N1 A/Puerto Rico/8/1934 (PR8). METHOD:Wild-type (WT) C57BL/6 mice were intranasally inoculated with S. pneumoniae serotype 6A to establish colonization and later infected with the influenza strain, PR8, resulting in invasive S. pneumoniae disease. The role of the IL-17A response in colonization and coinfection was investigated in WT, RoR?t-/- and RAG1-/- mice with antibody-mediated depletion of IL-17A (WT) and CD90 cells (RAG1-/-). RESULTS:RAG1-/- mice did not clear colonization and IL-17A neutralization impaired 6A clearance in WT mice. RoR?t-/- mice also had reduced clearance. S. pneumoniae-PR8 coinfection elicited a robust IL-17A response in the nasopharynx; IL-17A neutralization reduced S. pneumoniae invasive disease. RoR?t-/- mice also had reduced S. pneumoniae disease in a coinfection model. Depletion of CD90+ cells suppressed the IL-17A response and reduced S. pneumoniae invasion in RAG1-/- mice. CONCLUSION:Our data show that although IL-17A reduces S. pneumoniae colonization, coinfection with influenza virus elicits a robust innate IL-17A response that promotes inflammation and S. pneumoniae disease in the nasopharynx.

| S-EPMC6667796 | biostudies-literature

Pathogenesis and Treatment of Neurologic Diseases Associated With Mycoplasma pneumoniae Infection.

Project description:Mycoplasma pneumoniae is mainly recognized as a respiratory pathogen, although it is associated with the development of several extra-respiratory conditions in up to 25% of the cases. Diseases affecting the nervous system, both the peripheral (PNS) and the central nervous system (CNS), are the most severe. In some cases, particularly those that involve the CNS, M. pneumoniae-related neuropathies can lead to death or to persistent neurologic problems with a significant impact on health and a non-marginal reduction in the quality of life of the patients. However, the pathogenesis of most of the M. pneumoniae-related neuropathies remains undefined. The main aim of this paper is to discuss what is presently known regarding the pathogenesis and treatment of the most common neurologic disorders associated with M. pneumoniae infection. Unfortunately, the lack of knowledge of the true pathogenesis of most of the cases of M. pneumoniae-mediated neurological diseases explains why treatment is not precisely defined. However, antibiotic treatment with drugs that are active against M. pneumoniae and able to pass the blood-brain barrier is recommended, even though the best drug, dosage, and duration of therapy have not been established. Sporadic clinical reports seem to indicate that because immunity plays a relevant role in the severity of the condition and outcome, attempts to reduce the immune response can be useful. However, further studies are needed before the problem of the best therapy for M. pneumoniae-mediated neurological diseases can be efficiently solved.

| S-EPMC6255859 | biostudies-other

Climate variability and nonstationary dynamics of Mycoplasma pneumoniae pneumonia in Japan.

Project description:BackgroundA stationary association between climate factors and epidemics of Mycoplasma pneumoniae (M. pneumoniae) pneumonia has been widely assumed. However, it is unclear whether elements of the local climate that are relevant to M. pneumoniae pneumonia transmission have stationary signatures of climate factors on their dynamics over different time scales.MethodsWe performed a cross-wavelet coherency analysis to assess the patterns of association between monthly M. pneumoniae cases in Fukuoka, Japan, from 2000 to 2012 and indices for the Indian Ocean Dipole (IOD) and El Niño Southern Oscillation (ENSO).ResultsMonthly M. pneumoniae cases were strongly associated with the dynamics of both the IOD and ENSO for the 1-2-year periodic mode in 2005-2007 and 2010-2011. This association was non-stationary and appeared to have a major influence on the synchrony of M. pneumoniae epidemics.ConclusionsOur results call for the consideration of non-stationary, possibly non-linear, patterns of association between M. pneumoniae cases and climatic factors in early warning systems.

| S-EPMC3989333 | biostudies-literature

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