scholarly journals Moraxella Catarrhalis-Specific Th1 Cells in Bal Fluids of Chronic Obstructive Pulmonary Disease Patients

2009 ◽  
Vol 22 (4) ◽  
pp. 979-990 ◽  
Author(s):  
A. Amedei ◽  
C. Della Bella ◽  
E. Niccolai ◽  
N. Stanflin ◽  
M. Benagiano ◽  
...  
2005 ◽  
Vol 73 (6) ◽  
pp. 3471-3478 ◽  
Author(s):  
Timothy F. Murphy ◽  
Aimee L. Brauer ◽  
Christoph Aebi ◽  
Sanjay Sethi

ABSTRACT Moraxella catarrhalis is an important respiratory tract pathogen, causing otitis media in children and lower respiratory tract infections in adults with chronic obstructive pulmonary disease (COPD). Adults with COPD make antibody responses to M. catarrhalis following infection, but little is known about the identity of the antigens to which these antibodies are directed. In this study, 12 serum samples obtained from adults with COPD who had cleared M. catarrhalis from the respiratory tract following infection and who had developed new serum immunoglobulin G (IgG) to their infecting strain were subjected to a series of assays to identify the antigens to which potentially protective antibodies were directed. Sera were adsorbed with intact bacterial cells, and antibodies were eluted from the surfaces of the bacteria. Analysis by flow cytometry established that adsorption and elution effectively detected antibodies specifically directed to surface-exposed epitopes. Immunoblot assays of adsorbed and eluted serum fractions were performed with purified outer membranes and purified lipooligosaccharide of homologous infecting strains and with a series of mutants deficient in expression of individual outer membrane proteins (OMPs). While heterogeneity in antibody responses among individuals was observed, five major OMPs, UspA1, UspA2, Hag, TbpB, and OMP CD, were identified as targets of antibodies to surface epitopes in the majority of adults with COPD who cleared the organism. These results have important implications in understanding human immune responses to M. catarrhalis and in elucidating the elements of a protective immune response.


2005 ◽  
Vol 73 (12) ◽  
pp. 8161-8166 ◽  
Author(s):  
Timothy F. Murphy ◽  
Aimee L. Brauer ◽  
Christoph Aebi ◽  
Sanjay Sethi

ABSTRACT Moraxella catarrhalis is an important human mucosal pathogen causing otitis media in children and lower respiratory tract infection in adults with chronic obstructive pulmonary disease (COPD). Little is known about the mucosal antibody response to M. catarrhalis in adults with COPD. In this study, 10 pairs of well-characterized sputum supernatant samples from adults with COPD who had acquired and subsequently cleared M. catarrhalis from their respiratory tracts were studied in detail in an effort to begin to elucidate potentially protective immune responses. Flow cytometry analysis was used to study the distribution of immunoglobulin isotypes in paired preacquisition and postclearance sputum samples. The results showed that immunoglobulin A (IgA) is the predominant M. catarrhalis-specific immunoglobulin isotype and that the sputum IgA contains a secretory component, indicating that it is locally produced at the mucosal site. Most patients made new sputum IgA responses to the adhesins UspA1 and Hag, along with the surface protein UspA2. A smaller proportion of patients made new sputum IgA responses to the iron-regulated proteins TbpB and CopB and to lipooligosaccharide. These results have important implications in understanding the mucosal immune response to M. catarrhalis in the setting of COPD and in elucidating the elements of a protective immune response.


2020 ◽  
Vol 9 (12) ◽  
Author(s):  
Luke V. Blakeway ◽  
Aimee Tan ◽  
Ian R. Peak ◽  
John M. Atack ◽  
Kate L. Seib

Moraxella catarrhalis is a leading cause of otitis media and exacerbations of chronic obstructive pulmonary disease; however, its response to iron starvation during infection is not completely understood. Here, we announce a sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) data set describing the differential expression of the M. catarrhalis CCRI-195ME proteome under iron-restricted versus iron-replete conditions.


2003 ◽  
Vol 71 (3) ◽  
pp. 1288-1294 ◽  
Author(s):  
Timothy F. Murphy ◽  
Charmaine Kirkham ◽  
Dai-Fang Liu ◽  
Sanjay Sethi

ABSTRACT Moraxella catarrhalis is a common cause of lower respiratory tract infection in adults with chronic obstructive pulmonary disease (COPD). The antibody response to outer membrane protein (OMP) CD, a highly conserved surface protein of M. catarrhalis under consideration as a vaccine antigen, was studied in adults with COPD following 40 episodes of infection or colonization. Following infection or colonization, 9 of 40 patients developed new serum immunoglobulin G (IgG) to OMP CD, as measured by enzyme-linked immunosorbent assay. Adsorption assays revealed that a proportion of the serum IgG was directed toward surface-exposed epitopes on OMP CD in six of the nine patients who developed new IgG to OMP CD. Immunoblot assays with fusion peptide constructs indicated that the new antibodies that developed after infection or colonization recognized conformational epitopes, particularly in the carboxy region of the protein. Three of 28 patients developed new mucosal IgA to OMP CD in sputum supernatants. This study establishes that OMP CD is a target of a systemic and mucosal immune response following infection and colonization in some patients with COPD.


mBio ◽  
2016 ◽  
Vol 7 (2) ◽  
Author(s):  
Birendra Singh ◽  
Maria Alvarado-Kristensson ◽  
Martin Johansson ◽  
Oskar Hallgren ◽  
Gunilla Westergren-Thorsson ◽  
...  

ABSTRACTMoraxella catarrhalisis a human respiratory pathogen that causes acute otitis media in children and is associated with exacerbations in patients suffering from chronic obstructive pulmonary disease (COPD). The first step inM. catarrhaliscolonization is adherence to the mucosa, epithelial cells, and extracellular matrix (ECM). The objective of this study was to evaluate the role ofM. catarrhalisinteractions with collagens from various angles. Clinical isolates (n= 43) were tested for collagen binding, followed by a detailed analysis of protein-protein interactions using recombinantly expressed proteins.M. catarrhalis-dependent interactions with collagen produced by human lung fibroblasts and tracheal tissues were studied by utilizing confocal immunohistochemistry and high-resolution scanning electron microscopy. A mouse smoke-induced chronic obstructive pulmonary disease (COPD) model was used to estimate the adherence ofM. catarrhalisin vivo. We found that allM. catarrhalisclinical isolates tested adhered to fibrillar collagen types I, II, and III and network-forming collagens IV and VI. The trimeric autotransporter adhesinsubiquitoussurfaceproteinA2(UspA2) and UspA2H were identified as major collagen-binding receptors.M. catarrhaliswild type adhered to human tracheal tissue and collagen-producing lung fibroblasts, whereas UspA2 and UspA2H deletion mutants did not. Moreover, in the COPD mouse model, bacteria devoid of UspA2 and UspA2H had a reduced level of adherence to the respiratory tract compared to the adherence of wild-type bacteria. Our data therefore suggest that theM. catarrhalisUspA2 and UspA2H-dependent interaction with collagens is highly critical for adherence in the host and, furthermore, may play an important role in the establishment of disease.IMPORTANCEThe respiratory tract pathogenMoraxella catarrhalisadheres to the host by interacting with several components, including the ECM. Collagen accounts for 30% of total body proteins, and therefore, bacterial adherence to abundant host collagens mediates bacterial persistence and colonization. In this study, we characterized previously unknownM. catarrhalis-dependent interactions with host collagens and found that the trimeric autotransporter adhesinsubiquitoussurfaceproteinA2(UspA2) and UspA2H are highly important. Our observations also suggested that collagen-mediated adherence ofM. catarrhalisis indispensable for bacterial survival in the host, as exemplified by a mouse COPD model.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Lucio Malvisi ◽  
◽  
Laura Taddei ◽  
Aparna Yarraguntla ◽  
Tom M. A. Wilkinson ◽  
...  

Abstract Background Infection with Haemophilus influenzae (Hi) or Moraxella catarrhalis (Mcat) is a risk factor for exacerbation in chronic obstructive pulmonary disease (COPD). The ability to predict Hi- or Mcat-associated exacerbations may be useful for interventions developed to reduce exacerbation frequency. Methods In a COPD observational study, sputum samples were collected at monthly stable-state visits and at exacerbation during two years of follow-up. Bacterial species (Hi, Mcat) were identified by culture and quantitative PCR assay. Post-hoc analyses were conducted to assess: (1) first Hi- or Mcat-positive exacerbations given presence or absence of Hi or Mcat at the screening visit (stable-state timepoint); (2) first Hi- or Mcat-positive exacerbations given presence or absence of Hi or Mcat at stable timepoints within previous 90 days; (3) second Hi- or Mcat-positive exacerbations given presence or absence of Hi or Mcat at stable timepoints within previous 90 days. Percentages and risk ratios (RRs) with 95% confidence intervals were calculated. Results PCR results for analyses 1, 2 and 3 (samples from 84, 88 and 83 subjects, respectively) showed that the risk of an Hi- or Mcat-positive exacerbation is significantly higher if sputum sample was Hi- or Mcat-positive than if Hi- or Mcat-negative at previous stable timepoints (apart from Mcat in analysis 3); RRs ranged from 2.1 to 3.2 for Hi and 1.9 to 2.6 for Mcat.For all analyses, the percentage of Hi- or Mcat-positive exacerbations given previous Hi- or Mcat-positive stable timepoints was higher than the percentage of Hi- or Mcat-positive exacerbations if Hi- or Mcat-negative at previous stable timepoints. Percentage of Hi- or Mcat-positive exacerbations given previous Hi- or Mcat-negative stable timepoints was 26.3%–37.0% for Hi and 17.6%–19.7% for Mcat. Conclusions Presence of Hi or Mcat at a stable timepoint was associated with a higher risk of a subsequent Hi- or Mcat-associated exacerbation compared with earlier absence. However, a large percentage of Hi- or Mcat-associated exacerbations was not associated with Hi/Mcat detection at an earlier timepoint. This suggests that administration of an intervention to reduce these exacerbations should be independent of bacterial presence at baseline. Trial Registrationhttps://clinicaltrials.gov/; NCT01360398, registered May 25, 2011


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