Neutrophil-Mediated Lung Injury Both via TLR2-Dependent Production of IL-1α and IL-12 p40, and TLR2-Independent CARDS Toxin after Mycoplasma pneumoniae Infection in Mice

Tamiya, Shigeyuki; Yoshikawa, Eisuke; Ogura, Monami; Kuroda, Etsushi; Suzuki, Koichiro; Yoshioka, Yasuo

doi:10.1128/spectrum.01588-21

Cited by 16 publications

(8 citation statements)

References 49 publications

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“…Higher proportions of neutrophils were detected in the BALF of SMPP patients ( 14 ). In mice, neutrophils have been proved to mediate lung injury during the infection of MP ( 30 ). In a previous study, we found that both cell damage and neutrophils contribute to MP infection and cytokine expression ( 31 ).…”

Section: Discussionmentioning

confidence: 99%

Serum cytokine profiling reveals different immune response patterns during general and severe Mycoplasma pneumoniae pneumonia

Zhang

Dou

et al. 2022

Front. Immunol.

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Mycoplasma pneumoniae (MP) is an important human pathogen that mainly affects children causing general and severe Mycoplasma pneumoniae pneumonia (G/SMPP). In the present study, a comprehensive immune response data (33 cytokines) was obtained in school-age children (3–9 years old) during MPP, aiming to analyze the immune response patterns during MPP. At acute phase, changes of cytokines were both detected in GMPP (24/33) and SMPP (23/33) groups compared to the healthy group (p < 0.05), with 20 identical cytokines. Between MPP groups, the levels of 13 cytokines (IL-2, IL-10, IL-11, IL-12, IL-20, IL-28A, IL-32, IL-35, IFN-α2, IFN-γ, IFN-β, BAFF, and TSLP) were higher and three cytokines (LIGHT, OPN and CHI3L1) were lower in the SMPP group than in the GMPP group (p < 0.05). Function analysis reveals that macrophage function (sCD163, CHI3L1) are not activated in both MPP groups; difference in regulatory patterns of T cells (IL26, IL27, OPN, LIGHT) and defective activation of B cells (BAFF) were detected in the SMPP group compared to the GMPP group. Besides, the level of osteocalcin; sIL-6Rβ and MMP-2 are both decreased in MPP groups at acute and convalescent phases compared to the healthy group, among which the levels of sIL-6Rβ and MMP-2 showed negative correlations (p < 0.1) to the application of bronchial lavage in SMPP group, indicating their roles in the development of MPP. At the convalescent phase, more cytokines recovered in GMPP (18) than SMPP (11), revealing better controlled immune response during GMPP. These results reveal different immune response patterns during GMPP and SMPP. In addition, the differentiated cytokines may serve as potential indicators of SMPP; early intervention on immune response regulations may be helpful in reducing the severity of SMPP.

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Section: Discussionmentioning

confidence: 99%

Serum cytokine profiling reveals different immune response patterns during general and severe Mycoplasma pneumoniae pneumonia

Zhang

Dou

et al. 2022

Front. Immunol.

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“…Neutrophil infiltration is generally recognized as one of the features of Mp pneumonia. While neutrophils are not essential for the clearance of Mp from the lungs [ 9 , 10 ], in the situation of “hyperinflammation,” excessive accumulation of neutrophils might cause lung injury by releasing myeloperoxidase (MPO) and proteases [ 10 , 25 ]. To investigate whether AOFE reduces inflammation in Mp pneumonia, we first examined if the administration of AOFE had an adverse effect on mouse health by feeding mice daily with different doses of AOFE for 10 days.…”

Section: Resultsmentioning

confidence: 99%

“…Clinical studies have shown that increased accumulations of neutrophils and lymphocytes are associated with the severity of Mp pneumonia, and may contribute to the pathogenesis [ 25 , 31 ]. In an animal model of Mp pneumonia, Tamiya et al showed that depletion of neutrophils did not affect the number of Mp in the BALF, but significantly reduced tissue injury, indicating that neutrophils contribute to lung injury, but not Mp clearance [ 10 ]. Our data showed that AOFE administration significantly reduced the infiltration of neutrophils into the lungs, suggesting that lung injury may also be reduced.…”

Section: Discussionmentioning

confidence: 99%

“…Neutrophils are the major inflammatory cells recruited during the early stage of Mp pneumonia. Although neutrophils are phagocytic cells, they are not essential for the elimination of Mp from the lungs, and in contrast, neutrophils were shown to contribute to lung injury in Mp pneumonia [ 9 , 10 ]. Therefore, immunomodulatory agents that can inhibit neutrophil infiltration are likely to suppress the exacerbation of Mp pneumonia [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Aspergillus oryzae Fermentation Extract Alleviates Inflammation in Mycoplasma pneumoniae Pneumonia

Lee

Chen²,

Pi³

et al. 2023

Molecules

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The filamentous fungus Aspergillus oryzae, also known as koji mold, has been used for centuries in the production of fermented foods in East Asia. A. oryzae fermentation can produce enzymes and metabolites with various bioactivities. In this study, we investigated whether A. oryzae fermentation extract (AOFE) has any effect on Mycoplasma pneumoniae (Mp) pneumonia. We performed solid-state fermentation of A. oryzae and obtained the ethanol extract. AOFE was analyzed by HPLC, and the major component was identified to be kojic acid. In vitro, AOFE suppressed Mp growth and invasion into A549 lung epithelial cells as determined by the gentamicin protection assay. AOFE treatment also suppressed Mp-stimulated production of tumor necrosis factor (TNF)-α and interleukin (IL)-6 at mRNA and protein levels in murine MH-S alveolar macrophages. In a mouse model of Mp pneumonia, Mp infection induced a marked pulmonary infiltration of neutrophils, which was significantly reduced in mice pre-treated orally with AOFE. AOFE administration also suppressed the production of proinflammatory cytokines and chemokines in the lungs. Collectively, our results show that AOFE has the potential to be developed into a preventive/therapeutic agent for Mp pneumonia.

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“…The mechanism of neutrophil infiltration into the lungs in Mycoplasma pneumoniae pneumonia involves the excessive production of various inflammatory cytokines and chemokines. 29 Thus, we can infer that Mycoplasma pneumoniae infection impacts the increase of HBP. Further, we have adjusted the logistic regression models for probable pathogens to account for the direct microbial damage to the respiratory tract.…”

Section: Discussionmentioning

confidence: 97%

Heparin-Binding Protein: A Prognostic Biomarker Associated with Severe or Complicated Community-Acquired Pneumonia in Children

Li¹,

Xu²,

Wu³

et al. 2023

JIR

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Purpose Heparin-binding protein (HBP) is a novel biomarker for inflammatory diseases. This study aimed to investigate the role of serum HBP in community-acquired pneumonia (CAP) in children and the association of HBP with the severity and prognosis. Patients and Methods A total of 125 children with CAP admitted to the hospital were enrolled in this retrospective study. We analyzed the differences in clinical characteristics and examination findings between patients with different levels of HBP. The severe or complicated CAP was defined as having severe radiographic findings and/or systemic manifestations. Receiver operator characteristic (ROC) curves detected the performance of biomarkers in identifying patients with severe or complicated pneumonia. The multivariate logistic regression models assessed the association between HBP levels and the severity and prognosis. Finally, we constructed a predictive model based on HBP. Results The rate of severe or complicated CAP for patients with upper-quartile HBP concentration (≥60 ng/mL) was 54.8%, significantly higher than that of patients with lower HBP concentration (26.6%). The level of HBP is substantially correlated with neutrophil counts, C-reactive protein, erythrocyte sedimentation rate, and serum amyloid A protein (r = 0.31, 0.26, 0.36, and 0.26, respectively). HBP achieved the highest level of discrimination for severe or complicated CAP among the biomarkers. Higher HBP concentration (≥60 ng/mL) was associated with a three-fold higher risk of severe or complicated CAP (adjusted odds ratio = 3.11, p < 0.05). A predictive model including four characteristics (HBP, lactate dehydrogenase, age and non-viral infection) for predicting severe or complicated CAP (with area under the ROC curve = 0.75) was built to create a nomogram. Conclusion Substantially elevated serum HBP is significantly associated with severe or complicated CAP and poor prognosis in children. This finding warrants further investigation of the function of HBP in the pathogenesis of CAP.

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Neutrophil-Mediated Lung Injury Both via TLR2-Dependent Production of IL-1α and IL-12 p40, and TLR2-Independent CARDS Toxin after Mycoplasma pneumoniae Infection in Mice

Abstract: Although Mp-induced pneumonia is usually a self-limiting disease, refractory life-threatening pneumonia is often induced. In addition, the development of alternative therapeutic strategies for Mp is expected because of the emergence of antibiotic-resistant Mp.

Cited by 16 publications

References 49 publications

Serum cytokine profiling reveals different immune response patterns during general and severe Mycoplasma pneumoniae pneumonia

Serum cytokine profiling reveals different immune response patterns during general and severe Mycoplasma pneumoniae pneumonia

Aspergillus oryzae Fermentation Extract Alleviates Inflammation in Mycoplasma pneumoniae Pneumonia

Heparin-Binding Protein: A Prognostic Biomarker Associated with Severe or Complicated Community-Acquired Pneumonia in Children

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