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

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.

[1]  Deli Xin,et al.  Cell damage and neutrophils promote the infection of Mycoplasma pneumoniae and inflammatory response. , 2022, Microbial pathogenesis.

[2]  Jinyuan Y Fu,et al.  Metabolomic analysis reveals potential biomarkers and the underlying pathogenesis involved in Mycoplasma pneumoniae pneumonia , 2022, Emerging microbes & infections.

[3]  Chad W. MacPherson,et al.  Probiotics Exhibit Strain-Specific Protective Effects in T84 Cells Challenged With Clostridioides difficile-Infected Fecal Water , 2022, Frontiers in Microbiology.

[4]  Y. Yoshioka,et al.  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 , 2021, Microbiology spectrum.

[5]  Deli Xin,et al.  Mechanism of Infantile Feire Kechuan Oral Solution against Mycoplasma pneumoniae infection of A549 cells. , 2021, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[6]  Xu Wang,et al.  IL‐26 promotes the pathogenesis of malignant pleural effusion by enhancing CD4+IL‐22+ T‐cell differentiation and inhibiting CD8+ T‐cell cytotoxicity , 2021, Journal of leukocyte biology.

[7]  Hua Peng,et al.  LIGHT of pulmonary NKT cells annihilates tissue protective alveolar macrophages in augmenting severe influenza pneumonia. , 2021, Science bulletin.

[8]  Yimou Wu,et al.  Mycoplasma pneumoniae lipids license TLR‐4 for activation of NLRP3 inflammasome and autophagy to evoke a proinflammatory response , 2020, Clinical and experimental immunology.

[9]  Zhengrong Chen,et al.  The diagnostic value of serological tests and real-time polymerase chain reaction in children with acute Mycoplasma pneumoniae infection , 2020, Annals of translational medicine.

[10]  Yuyun Li,et al.  The clinical significance of IL-6 s and IL-27 s in Bronchoalveolar lavage fluids from children with mycoplasma pneumoniae pneumonia , 2019, BMC Infectious Diseases.

[11]  M. Vargas,et al.  Drastically elevated levels of Interleukin-6 and its soluble receptor complex in COVID-19 patients with acute respiratory distress , 2020, Clinical and Medical Investigations.

[12]  G. Cheng,et al.  Cytokine signatures associate with disease severity in children with Mycoplasma pneumoniae pneumonia , 2019, Scientific Reports.

[13]  Dan Li,et al.  Allele-specific real-time PCR testing for minor macrolide-resistant Mycoplasma Pneumoniae , 2019, BMC Infectious Diseases.

[14]  T. Aune,et al.  Biological Effects of IL-26 on T Cell-Mediated Skin Inflammation, Including Psoriasis. , 2019, The Journal of investigative dermatology.

[15]  G. Ma,et al.  HDAC5 promotes Mycoplasma pneumoniae‐induced inflammation in macrophages through NF‐&kgr;B activation☆ , 2019, Life sciences.

[16]  R. Hendriks,et al.  Antibodies to Protein but Not Glycolipid Structures Are Important for Host Defense against Mycoplasma pneumoniae , 2018, Infection and Immunity.

[17]  Q. Shu,et al.  Mycoplasma pneumoniae induces allergy by producing P1-specific immunoglobulin E. , 2018, Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology.

[18]  G. Cheng,et al.  Interleukin 17A as a good predictor of the severity of Mycoplasma pneumoniae pneumonia in children , 2017, Scientific Reports.

[19]  S. Holland,et al.  A biallelic mutation in IL6ST encoding the GP130 co-receptor causes immunodeficiency and craniosynostosis , 2017, The Journal of experimental medicine.

[20]  Jianming Zhou,et al.  Utility of Assessing Cytokine Levels for the Differential Diagnosis of Pneumonia in a Pediatric Population* , 2017, Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

[21]  G. Cheng,et al.  Transcriptome analysis of bronchoalveolar lavage fluid from children with severe Mycoplasma pneumoniae pneumonia reveals novel gene expression and immunodeficiency , 2017, Human Genomics.

[22]  Zhimin Chen,et al.  Cytokines as the good predictors of refractory Mycoplasma pneumoniae pneumonia in school-aged children , 2016, Scientific Reports.

[23]  Yimou Wu,et al.  Insights into the pathogenesis of Mycoplasma pneumoniae , 2016, Molecular medicine reports.

[24]  T. Kishaba Community-Acquired Pneumonia Caused by Mycoplasma pneumoniae: How Physical and Radiological Examination Contribute to Successful Diagnosis , 2016, Front. Med..

[25]  Takashi Shimizu Inflammation-inducing Factors of Mycoplasma pneumoniae , 2016, Front. Microbiol..

[26]  Tingting Wang,et al.  Imbalance of peripheral blood Th17 and Treg responses in children with refractory Mycoplasma pneumoniae pneumonia. , 2016, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy.

[27]  R. Dumke,et al.  Antibody Response to Mycoplasma pneumoniae: Protection of Host and Influence on Outbreaks? , 2016, Front. Microbiol..

[28]  Zhengrong Chen,et al.  Role of the Mycoplasma pneumoniae/Interleukin-8/Neutrophil Axis in the Pathogenesis of Pneumonia , 2016, PloS one.

[29]  Zhimin Chen,et al.  Altered cytokine levels in bronchoalveolar lavage fluids from patients with mycoplasma pneumonia infection , 2016 .

[30]  M. Croft,et al.  Tumor necrosis factor superfamily 14 (LIGHT) controls thymic stromal lymphopoietin to drive pulmonary fibrosis. , 2015, The Journal of allergy and clinical immunology.

[31]  Zhi-min Chen,et al.  Increased T cell activation in BALF from children with Mycoplasma pneumoniae pneumonia , 2015, Pediatric pulmonology.

[32]  Zhengrong Chen,et al.  Clinical and laboratory profiles of refractory Mycoplasma pneumoniae pneumonia in children. , 2014, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[33]  K. Nakata,et al.  Novel aspects on the pathogenesis of Mycoplasma pneumoniae pneumonia and therapeutic implications , 2014, Front. Microbiol..

[34]  Rachelle W Johnson,et al.  The Primary Function of gp130 Signaling in Osteoblasts Is To Maintain Bone Formation and Strength, Rather Than Promote Osteoclast Formation , 2014, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[35]  A. Baker,et al.  N-Terminal Truncated Intracellular Matrix Metalloproteinase-2 Induces Cardiomyocyte Hypertrophy, Inflammation and Systolic Heart Failure , 2013, PloS one.

[36]  M. Kaplan,et al.  Innate Stat3-mediated induction of the antimicrobial protein Reg3γ is required for host defense against MRSA pneumonia , 2013, The Journal of experimental medicine.

[37]  M. Audran,et al.  IL-26 Is Overexpressed in Rheumatoid Arthritis and Induces Proinflammatory Cytokine Production and Th17 Cell Generation , 2012, PLoS biology.

[38]  O. Polašek,et al.  Mycoplasma pneumoniae in adult community-acquired pneumonia increases matrix metalloproteinase-9 serum level and induces its gene expression in peripheral blood mononuclear cells , 2012, Medical science monitor : international medical journal of experimental and clinical research.

[39]  A. Meryk,et al.  Cutting Edge: Inhibition of IL-6 Trans-Signaling Protects from Malaria-Induced Lethality in Mice , 2012, The Journal of Immunology.

[40]  S. Kamiya,et al.  Identification of a mechanism for lung inflammation caused by Mycoplasma pneumoniae using a novel mouse model. , 2011, Results in immunology.

[41]  Mingjie Ding,et al.  [Th1/Th2 immune response in bronchoalveolar lavage fluid in children with severe Mycoplasma pneumoniae pneumonia]. , 2011, Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics.

[42]  Ning Li,et al.  Distribution of Tuvaella brachiopod fauna and its tectonic significance , 2011 .

[43]  D. Chaplin,et al.  Critical Role of Macrophages and Their Activation via MyD88-NFκB Signaling in Lung Innate Immunity to Mycoplasma pneumoniae , 2010, PloS one.

[44]  T. van der Poll,et al.  Osteopontin promotes host defense during Klebsiella pneumoniae-induced pneumonia , 2010, European Respiratory Journal.

[45]  M. Narita Pathogenesis of extrapulmonary manifestations of Mycoplasma pneumoniae infection with special reference to pneumonia , 2010, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy.

[46]  M. Morozumi,et al.  Macrolide-resistant Mycoplasma pneumoniae: characteristics of isolates and clinical aspects of community-acquired pneumonia , 2010, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy.

[47]  B. Lambrecht,et al.  Osteopontin has a crucial role in allergic airway disease through regulation of dendritic cell subsets , 2007, Nature Medicine.

[48]  清水 隆 A dipalmitoylated lipoprotein from Mycoplasma pneumoniae activates NF-κB through TLR1, TLR2, and TLR6 , 2006 .

[49]  D. Lawrence,et al.  TWEAK Attenuates the Transition from Innate to Adaptive Immunity , 2005, Cell.

[50]  Takashi Shimizu,et al.  A Dipalmitoylated Lipoprotein from Mycoplasma pneumoniae Activates NF-κB through TLR1, TLR2, and TLR61 , 2005, The Journal of Immunology.

[51]  K. Hoek,et al.  A role for the Mycoplasma pneumoniae adhesin P1 in interleukin (IL)-4 synthesis and release from rodent mast cells. , 2005, Microbial pathogenesis.

[52]  Ken B. Waites,et al.  Mycoplasma pneumoniae and Its Role as a Human Pathogen , 2004, Clinical Microbiology Reviews.

[53]  D. Talkington,et al.  Cytokines in Mycoplasma pneumoniae infections. , 2004, Cytokine & growth factor reviews.

[54]  K. Waites New concepts of Mycoplasma pneumoniae infections in children , 2003, Pediatric pulmonology.

[55]  M. Rincón,et al.  The two faces of IL-6 on Th1/Th2 differentiation. , 2002, Molecular immunology.

[56]  D. Talkington,et al.  Regulation of Proinflammatory Cytokines in Human Lung Epithelial Cells Infected with Mycoplasma pneumoniae , 2002, Infection and Immunity.

[57]  Mark A. Hall,et al.  Interleukin-11 Signals through the Formation of a Hexameric Receptor Complex* , 2000, The Journal of Biological Chemistry.

[58]  A. O’Regan,et al.  Osteopontin augments CD3‐mediated interferon‐γ and CD40 ligand expression by T cells, which results in IL‐12 production from peripheral blood mononuclear cells , 2000, Journal of leukocyte biology.

[59]  G. Biberfeld Macrophage migration inhibition in response to experimental mycoplasma pneumoniae infection in the hamster , 1973, The Journal of Immunology.