Claus Moser - Academia.edu (original) (raw)

Papers by Claus Moser

Journal of Cystic Fibrosis, Jun 1, 2009

Background: The aim of this study was to determine the prevalence of different autoantibodies (aA... more Background: The aim of this study was to determine the prevalence of different autoantibodies (aAbs) in adult French cystic fibrosis (CF) patients and to look for a correlation between autoimmunity, patient characteristics and survival. Methods: The sera of 144 patients were screened for a wide range of Abs. Clinical, biological and bacteriological characteristics and CFTR genotype were recorded and progression of lung disease was examined. Results: One hundred and thirteen patients (78.5%) displayed one or several aAbs, predominantly IgA anti-Saccharomyces cerevisiae antibodies (ASCA IgA) (43.7%) and anti-neutrophil cytoplasmic antibodies (ANCA) (40%), of which 59% showed bactericidal/permeability-increasing protein (BPI) specificity. The presence of BPI-ANCA was associated with the number of antibiotic courses, low body mass index, P aeruginosa colonisation, presence of resistant P aeruginosa, low FEV1, CFrelated liver disease, hypergammaglobulinaemia, male gender and inflammatory syndrome. The presence of ASCA IgA was correlated with male gender and hypergammaglobulinaemia. Forty-one patients presented chronic respiratory failure and/or requested lung transplantation or died during follow-up. These events were more frequent in patients with BPI-ANCA or ASCA IgA. Conclusion: These findings confirmed the high frequency of aAbs in CF, particularly BPI-ANCA and ASCA IgA, and the link between BPI-ANCA, severity of lung disease and CF prognosis. Supported by: Association Recherche en Médecine Interne.

Biomedicines, Aug 24, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Microbiology, Jul 30, 2009

Polymorphonuclear neutrophilic leukocytes (PMNs) play a central role in innate immunity, where th... more Polymorphonuclear neutrophilic leukocytes (PMNs) play a central role in innate immunity, where they dominate the response to infections, in particular in the cystic fibrosis lung. PMNs are phagocytic cells that produce a wide range of antimicrobial agents aimed at killing invading bacteria. However, the opportunistic pathogen Pseudomonas aeruginosa can evade destruction by PMNs and thus cause persistent infections. In this study, we show that biofilm cells of P. aeruginosa recognize the presence of attracted PMNs and direct this information to their fellow bacteria through the quorum sensing (QS) signalling system. The bacteria respond to the presence of PMNs by upregulating synthesis of a number of QS-controlled virulence determinants including rhamnolipids, all of which are able to cripple and eliminate cells of the host defence. Our in vitro and in vivo analyses support a 'launch a shield' model by which rhamnolipids surround the biofilm bacteria and on contact eliminate incoming PMNs. Our data strengthen the view that cross-kingdom communication plays a key role in P. aeruginosa recognition and evasion of the host defence.

Journal of Cystic Fibrosis, Jun 1, 2014

Journal of Cystic Fibrosis, Jun 1, 2010

Apmis, Sep 1, 2003

The purpose of the present study was to investigate whether NK cells from resistant C3H/HeN mice ... more The purpose of the present study was to investigate whether NK cells from resistant C3H/HeN mice and susceptible BALB/c mice showed different release of cytokines and expression of surface molecules during chronic P. aeruginosa lung infection using alginate-embedded P. aeruginosa mimicking the infection in cystic fibrosis. Lung cell suspensions were depleted of lymphocytes by magnetic cell sorting. The concentrations of IFN-g, IL-1b and GM-CSF were estimated by ELISA at day 1 and 2 after infection. Non-infected mice were used as controls. Flow cytometry was used to estimate the surface expression of the LFA-1 and Fc receptors on NK cells. At day 2, IFN-g levels increased in C3H/HeN mice but decreased in BALB/c mice. The GM-CSF levels increased only in the C3H/HeN mice at day 1 and 2. Surface expression of LFA-1 on the NK cells was higher in C3H/HeN mice at day 1 and 2. In contrast, the expression of Fc receptors was significantly lower on NK cells in C3H/ HeN mice at day 1 and 2. In conclusion, the present results show phenotypic differences in NK cells in the two mice strains in chronic P. aeruginosa lung infection, indicating different modulating effects in the Th1/Th2 balance.

Journal of Cystic Fibrosis, Aug 1, 2006

Background: Chronic Pseudomonas aeruginosa lung infection is the major reason for premature death... more Background: Chronic Pseudomonas aeruginosa lung infection is the major reason for premature death in patients with cystic fibrosis (CF). Infected patients experience a progressive deterioration of the lung tissue caused by a persistent accumulation of PMNs. We investigated if the pulmonary accumulation of PMNs is reflected as a migration of PMNs through the blood in chronically infected CF patients. Methods: Blood and sputum samples from 37 stable, chronically (CF + P) and 6 non-infected (CF À P) CF patients without exacerbations were compared using FACS, leukocyte counting, and ELISA. Within the CF + P patients, the blood parameters were compared to the lung function (FEV1 and FVC) and to the sputum. Similar measurements were performed on 15 chronically infected CF patients before and after elective antibiotic treatment. Results: In the CF + P patients the concentration of G-CSF in the sera and PMNs in the blood was increased and correlated to poor lung function. However, only the concentration of G-CSF in the sera was correlated to the concentration of TNF-a in the sputum. After the antibiotic treatment, the lung function was improved and the concentration of PMNs in the blood and G-CSF in the sera was reduced. Conclusion: G-CSF in the sera may contribute to the pulmonary inflammation in CF patients with chronic P. aeruginosa lung infection by regulating the number of PMNs available for migration and may be considered as an indicator of clinical status.

Apmis, Oct 12, 2020

IL‐2 is a pro‐inflammatory and a Th1 inducing cytokine, which is important for activation of the ... more IL‐2 is a pro‐inflammatory and a Th1 inducing cytokine, which is important for activation of the cell‐mediated immunity. IL‐2 in serum and sputum has been observed to be reduced in cystic fibrosis (CF) patients. The present IL‐2 treatment study of Pseudomonas aeruginosa (PA) lung infected mice was performed in order to evaluate the effect of IL‐2 supplement. One hundred‐and‐twenty female BALB/c mice were divided into three groups: 1) IL‐2 treatment/infection (TIG), 2) non‐treatment/infection (NTIG), and 3) IL‐2 treatment/non‐infection (TNIG). The mice were challenged intra‐tracheally with PA (PAO579) embedded in seaweed alginate to resemble the biofilm mode of growth. At day 0 and 1, the treatment groups received IL‐2 s.c. Mice were killed on day 1 or 2, and cytokine production, lung pathology, and quantitative lung bacteriology were estimated. IL‐2 treatment of infected mice reduced the number of mice with signs of macroscopic lung pathology at day 2 (p < 0.05). The reduced macroscopic pathology was paralleled by a reduced IL‐1β and TNF‐α. In contrast, an increased PMN response at day 2 was observed in the IL‐2 treated mice (p < 0.01). This was preceded by a significantly higher degree of microscopic inflammation at day 1 (p < 0.02). The IL‐12 levels decreased in both groups of infected mice at day 2 (p < 0.01), however, significantly more in the IL‐2 treated mice (p < 0.02). In accordance, but surprisingly, IFN‐γ was significantly reduced in the IL‐2 treated PA infected group at day 2 (p < 0.05). The present results indicate that early IL‐2 treatment prolongs the PMN response but also reduces pro‐inflammatory IL‐1β and TNF‐α and macroscopic signs of pathology.

British Journal of Dermatology, Jun 1, 1997

Subcutaneous lesions were seen in three of 13 neutropenia patients who had Stenotrophomonas (Xant... more Subcutaneous lesions were seen in three of 13 neutropenia patients who had Stenotrophomonas (Xanthomonas) maltophilia bacteraemia. The characteristic clinical presentation resembled leukaemic infiltrates, and were different from deep ulcers or subcutaneous nodules caused by Pseudomonas aeruginosa. The three patients had acute leukaemia and were treated with intensive combination chemotherapy. All had previously been treated with broad-spectrum antibiotics, and each patient recovered after proper combination antibiotic treatment given according to sensitivity testing.

Clinical and Experimental Immunology, Feb 1, 2002

Repeated challenge with antigen is involved in the pathogenesis of a variety of pulmonary disease... more Repeated challenge with antigen is involved in the pathogenesis of a variety of pulmonary diseases. Patients with cystic fibrosis (CF) experience recurrent pulmonary colonization with Pseudomonas aeruginosa before establishment of chronic lung infection. To mimic recurrent lung infections in CF patients, the lungs of susceptible BALB/c mice were re-infected with P. aeruginosa 14 days after the initial infection. Singly-infected BALB/c mice, as well as non-infected mice, were used as controls. Decreased mortality and milder lung inflammation in re-infected BALB/c mice, as well as a tendency for improved clearance of bacteria, was observed when compared with singly-infected mice. The improved outcome in re-infected mice correlated with changes in CD4 cell numbers. Surface expression of LFA-1 on pulmonary CD4 cells was increased in re-infected compared with singly-infected mice. Moreover, resistance to re-infection was paralleled by a shift towards a Th1-dominated response and increased IL-12 production. No significant increase in serum IgG was observed in the re-infected mice. In conclusion, these results indicate a protective role for a Th1-dominated response, independent of antibody production, in chronic P. aeruginosa lung infection in CF.

Trends in Microbiology, Sep 1, 2013

This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit: http://www.elsevier.com/authorsrights

Apmis, Oct 18, 2021

Infective endocarditis (IE) is a heart valve infection with high mortality rates. IE results from... more Infective endocarditis (IE) is a heart valve infection with high mortality rates. IE results from epithelial lesions, inducing sterile healing vegetations consisting of platelets, leucocytes, and fibrin that are susceptible for colonization by temporary bacteremia. Clinical testing of new treatments for IE is difficult and fast models sparse. The present study aimed at establishing an in vitro vegetation simulation IE model for fast screening of novel treatment strategies. A healing promoting platelet and leucocyte‐rich fibrin patch was used to establish an IE organoid‐like model by colonization with IE‐associated bacterial isolates Staphylococcus aureus, Streptococcus spp (S. mitis group), and Enterococcus faecalis. The patch was subsequently exposed to tobramycin, ciprofloxacin, or penicillin. Bacterial colonization was evaluated by microscopy and quantitative bacteriology. We achieved stable bacterial colonization on the patch, comparable to clinical IE vegetations. Microscopy revealed uneven, biofilm‐like colonization of the patch. The surface‐associated bacteria displayed increased tolerance to antibiotics compared to planktonic bacteria. The present study succeeded in establishing an IE simulation model with the relevant pathogens S. aureus, S. mitis group, and E. faecalis. The findings indicate that the IE model mirrors the natural IE process and has the potential for fast screening of treatment candidates.

Journal of Investigative Medicine, Oct 1, 2021

Necrotizing soft-tissue infection (NSTI) is a rare, severe, and fast-progressing bacterial infect... more Necrotizing soft-tissue infection (NSTI) is a rare, severe, and fast-progressing bacterial infection associated with a high risk of developing sepsis or septic shock. Increasing evidence indicates that oxidative stress is crucial in the development and progression of sepsis, but its role in NSTI specifically has not been investigated. Some patients with NSTI receive hyperbaric oxygen (HBO 2) treatment as the restoration of oxidative stress balance is considered an important mechanism of action, which HBO 2 facilitates. However, a gap in knowledge exists regarding the effect of HBO 2 treatment on oxidative stress in patients with NSTI. In the present observational study, we aimed to investigate HBO 2 treatment effects on known markers of oxidative stress in patients with NSTI. We measured plasma myeloperoxidase (MPO), superoxide dismutase (SOD), heme oxygenase-1 (HO-1) and nitrite+nitrate in 80 patients with NSTI immediately before and after their first HBO 2 treatment, and on the following day. We found that HBO 2 treatment was associated with a significant increase in MPO and SOD by a median of 3.4 and 8.8 ng/mL, respectively. Moreover, we observed an HBO 2 treatment-associated increase in HO-1 in patients presenting with septic shock (n=39) by a median of 301.3 pg/mL. All markers were significantly higher in patients presenting with septic shock compared to patients without shock, and all markers correlated with disease severity. High baseline SOD was associated with 90-day mortality. In conclusion, HBO 2 treatment was associated with an increase in MPO and SOD in patients with NSTI, and oxidative stress was more pronounced in patients with septic shock. How might these results change the focus of research or clinical practice? ► These findings increase our understanding of both NSTI pathophysiology and the mechanism of action of HBO 2 treatment.

BMC Infectious Diseases, Mar 27, 2017

Background: Culturing has long been the gold standard for detecting aetiologic agents in bacteria... more Background: Culturing has long been the gold standard for detecting aetiologic agents in bacterial infections. In some cases, however, culturing fails to detect the infection. To further investigate culture-negative samples, amplification and subsequent sequencing of the 16S rRNA gene is often applied. The aim of the present study was to compare the current method used at our Department of Clinical Microbiology, based on the MicroSeq ID system (Applied Biosystems, USA) with the Universal Microbe Detection (UMD) SelectNA kit (Molzym, Germany). Methods: 76 culture-negative samples were first processed with the MicroSeq ID analysis, where total DNA was extracted and the 16S gene amplified and sequenced with the MicroSeq ID system. Samples were subsequently processed with the UMD SelectNA analysis, where human DNA was removed during the DNA extraction procedure and the 16S gene amplified in a real-time PCR and sequenced. Results: 22 of 76 samples (28.9%) were positive for bacteria with the UMD SelectNA, which was significantly more (p = 0.0055) than the MicroSeq ID where 11 of 76 samples (14.5%) were positive. The UMD SelectNA assay identified more relevant bacterial pathogens than the MicroSeq ID analysis (p = 0.0233), but also found a number of species that were considered contaminations. Conclusions: The UMD SelectNA assay was valuable for the identification of pathogens in culture-negative samples; however, due to the sensitive nature of the assay, extreme care is suggested in order to avoid false positives.

Molecular Microbiology, Feb 1, 2009

Polymorphonuclear neutrophils are the most important mammalian host defence cells against infecti... more Polymorphonuclear neutrophils are the most important mammalian host defence cells against infections with Pseudomonas aeruginosa. Screening of a signature tagged mutagenesis library of the non-piliated P. aeruginosa strain TBCF10839 uncovered that transposon inactivation of its pilY1 gene rendered the bacterium more resistant against killing by neutrophils than the wild type and any other of the more than 3000 tested mutants. Inactivation of pilY1 led to the loss of twitching motility in twitching-proficient wild-type PA14 and PAO1 strains, predisposed to autolysis and impaired the secretion of quinolones and pyocyanin, but on the other hand promoted growth in stationary phase and bacterial survival in murine airway infection models. The PilY1 population consisted of a major full-length and a minor shorter PilY1* isoform. PilY1* was detectable in small extracellular quinolone-positive aggregates, but not in the pilus. P. aeruginosa PilY1 is not an adhesin on the pilus tip, but assists in pilus biogenesis, twitching motility, secretion of secondary metabolites and in the control of cell density in the bacterial population.

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Nature Reviews Microbiology, Feb 3, 2022

Chronic infections caused by microbial biofilms represent an important clinical challenge. The re... more Chronic infections caused by microbial biofilms represent an important clinical challenge. The recalcitrance of microbial biofilms to antimicrobials and to the immune system is a major cause of persistence and clinical recurrence of these infections. In this Review, we present the extent of the clinical problem, and the mechanisms underlying the tolerance of biofilms to antibiotics and to host responses. We also explore the role of biofilms in the development of antimicrobial resistance mechanisms.

Springer series on biofilms, 2022