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Cajander, S., Rasmussen, G., Tina, E., Magnuson, A., Söderquist, B., Källman, J. & Strålin, K. (2018). Dynamics of monocytic HLA-DR expression differs between bacterial etiologies during the course of bloodstream infection. PLoS ONE, 13(2), Article ID e0192883.
Open this publication in new window or tab >>Dynamics of monocytic HLA-DR expression differs between bacterial etiologies during the course of bloodstream infection
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2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 2, article id e0192883Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: In the pathogenesis of sepsis, activation of both pro- and anti-inflammatory responses are key components, but knowledge is lacking on the association between bacterial etiology and development of dysregulated responses with sustained immunosuppression. The aim of this study was to evaluate how the immunosupression marker HLA-DR on monocytes (mHLA-DR) is associated with bacterial etiology and markers of inflammation during the clinical trajectory of bloodstream infection (BSI).

METHODS: Ninety-one adults, predominantly non-ICU patients, with BSI caused by Streptococcus pneumoniae (n = 27), Staphylococcus aureus (n = 22), Escherichia coli/Klebsiella pneumoniae (n = 23), and other species (n = 19) were prospectively included, and sampled on admission (day 0) and on days 1-2, 3, 7±1, 14±2, and 28±4.

RESULTS: The dynamics of mHLA-DR, measured by flow cytometry, differed significantly between etiology groups (p<0.001). Patients with S. pneumoniae and S. aureus BSI demonstrated low initial mHLA-DR, with the S. aureus group showing delayed recovery over time. Eleven patients (55% S. aureus) had negative outcome (secondary bacteremia or death) and they demonstrated sustained C-reactive protein elevation, neutrophilia, lymphocytopenia, and loss of mHLA-DR.

CONCLUSIONS: Dynamics of mHLA-DR varied according to the bacterial etiology of infection, with delayed recovery in patients with S. aureus BSI. Patients with negative outcome showed sustained CRP elevation, neutrophilia, lymphocytopenia, and low levels of mHLA-DR, supporting the theory of a dysregulated host response with persistent inflammation and immunosuppression in late stages of deleterious sepsis.

Place, publisher, year, edition, pages
Public Library of Science, 2018
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-65287 (URN)10.1371/journal.pone.0192883 (DOI)000425604300071 ()29466395 (PubMedID)2-s2.0-85042254936 (Scopus ID)
Note

Funding Agencies:

Research Committee of Örebro County Council  

ALF research funding (Örebro University)  

Nyckelfonden (Örebro University Hospital)  

ALF research funding (Örebro) 

Available from: 2018-02-27 Created: 2018-02-27 Last updated: 2018-09-13Bibliographically approved
Lindell, F., Söderquist, B., Sundman, K., Olaison, L. & Källman, J. (2018). Prosthetic valve endocarditis caused by Propionibacterium species: a national registry-based study of 51 Swedish cases. European Journal of Clinical Microbiology and Infectious Diseases, 37(4), 765-771
Open this publication in new window or tab >>Prosthetic valve endocarditis caused by Propionibacterium species: a national registry-based study of 51 Swedish cases
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2018 (English)In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 37, no 4, p. 765-771Article in journal (Refereed) Published
Abstract [en]

Propionibacterium spp. are a rare cause of infective endocarditis (IE). The diagnosis is difficult because the bacteria are slow-growing and growth in blood cultures is often misinterpreted as contamination from the skin flora. The aim of this study was to describe all cases of Propionibacterium spp. endocarditis in the Swedish national registry of IE. The registry was searched for all cases of IE from 1995 to 2016 caused by Propionibacterium spp. Data concerning clinical characteristics, treatment, and outcome were registered. A total of 51 episodes of definitive prosthetic valve endocarditis (PVE) caused by Propionibacterium spp. were identified, comprising 8% of cases of PVE during the study period. Almost all cases (n = 50) were male. The median time from surgery to diagnosis of IE was 3 years. Most patients were treated mainly with beta-lactams, partly in combination with aminoglycosides. Benzyl-penicillin was the most frequently used beta-lactam. A total of 32 patients (63%) underwent surgery. Overall, 47 patients (92.1%) were cured, 3 (5.9%) suffered relapse, and 1 (2.0%) died during treatment. IE caused by Propionibacterium spp. almost exclusively affects men with a prosthetic valve and findings of Propionibacterium spp. in blood cultures in such patients favors suspicion of a possible diagnosis of IE. In patients with prosthetic valves, prolonged incubation of blood cultures up to 14 days is recommended. The prognosis was favorable, although a majority of patients required cardiac surgery during treatment. Benzyl-penicillin should be the first-line antibiotic treatment option for IE caused by Propionibacterium spp.

Place, publisher, year, edition, pages
Springer, 2018
National Category
Infectious Medicine Microbiology in the medical area
Identifiers
urn:nbn:se:oru:diva-64849 (URN)10.1007/s10096-017-3172-8 (DOI)000428247300021 ()29380224 (PubMedID)2-s2.0-85041116111 (Scopus ID)
Available from: 2018-02-07 Created: 2018-02-07 Last updated: 2018-08-20Bibliographically approved
Rasmussen, G., Cajander, S., Bäckman, A., Källman, J., Söderquist, B. & Strålin, K. (2017). Expression of HLA-DRA and CD74 mRNA in whole blood during the course of complicated and uncomplicated Staphylococcus aureus bacteremia. Microbiology and immunology, 61(10), 442-451
Open this publication in new window or tab >>Expression of HLA-DRA and CD74 mRNA in whole blood during the course of complicated and uncomplicated Staphylococcus aureus bacteremia
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2017 (English)In: Microbiology and immunology, ISSN 0385-5600, E-ISSN 1348-0421, Vol. 61, no 10, p. 442-451Article in journal (Refereed) Published
Abstract [en]

To improve management of Staphylococcus aureus bacteremia (SAB), better understanding of host-pathogen interactions is needed. In vitro studies have shown that S. aureus bacteria induce dose-dependent immunosuppression that is evidenced by reduced expression of major histocompatibility complex (MHC) class II on antigen presenting cells. Thus, the aim of this study was to determine whether expression of the MHC class II-related genes HLA-DRA and CD74 is more greatly reduced in complicated SAB, with its probable higher loads of S. aureus, than in uncomplicated SAB. Adult patients with SAB were prospectively included and blood samples taken on the day of confirmation of SAB (Day 1) and on Days 2, 3, 5 and 7. HLA-DRA and CD74 mRNA expression was determined by quantitative reverse transcription PCR. Sepsis was defined according to the Sepsis-3 classification and SAB was categorized as complicated in patients with deep-seated infection and/or hematogenous seeding. Twenty patients with SAB were enrolled and samples obtained on all assessment days. HLA-DRA and CD74 expression did not differ significantly between patients with SAB and sepsis (n=13) and those without sepsis (n=7) on any assessment day. However, patients with complicated SAB (n=14) had significantly weaker HLA-DRA expression on all five assessment days than patients with uncomplicated SAB (n=6). Additionally, they tended to have weaker CD74 expressions. Neutrophil, monocyte and leukocyte counts did not differ significantly between complicated and uncomplicated SAB. In conclusion, patients with complicated SAB show weaker HLA-DRA expression than those with uncomplicated SAB during the first week of bacteremia.

Place, publisher, year, edition, pages
Wiley-Blackwell Publishing Asia, 2017
Keywords
CD74, HLA-DRA, sepsis, Staphylococcus aureus
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:oru:diva-62068 (URN)10.1111/1348-0421.12533 (DOI)000412860400005 ()28862321 (PubMedID)2-s2.0-85032877412 (Scopus ID)
Note

Funding Agency:

Research Committee of Örebro County Council

Available from: 2017-10-30 Created: 2017-10-30 Last updated: 2018-08-07Bibliographically approved
Ahlsson, A., Friberg, Ö. & Källman, J. (2016). An angry cat causing Pasteurella multocida endocarditis and aortic valve replacement: A case report. International journal of surgery case reports, 24, 91-93
Open this publication in new window or tab >>An angry cat causing Pasteurella multocida endocarditis and aortic valve replacement: A case report
2016 (English)In: International journal of surgery case reports, ISSN 2210-2612, E-ISSN 2210-2612, Vol. 24, p. 91-93Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: Cat bite infections usually involve a mix of anaerobic and aerobic bacteria including species of Pasteurella, Streptococcus, Staphylococcus, Bacteroides, and Fusobacterium. We report a case of Pasteurella multocida infection from cat bites leading to endocarditis and subsequent aortic valve replacement.

PRESENTATION OF CASE: A 70-year-old male was admitted because of fever, tachycardia, and malaise. He had a history of alcohol abuse and was living alone with a cat in a rural area. A sepsis of unknown origin was suspected, and intravenous treatment with gentamicin and cefotaxime was initiated. Blood cultures yielded Pasteurella multocida, and the patient history revealed repeated cat bites. After four days, the patient was discharged with oral penicillin V treatment. Two weeks later, the patient returned with fever and a new systolic murmur. An aortic valve endocarditis was diagnosed, and it became clear that the patient had not completed the prescribed penicillin V treatment. The patient underwent a biological aortic valve replacement with debridement of an annular abscess, and the postoperative course was uneventful.

DISCUSSION: Endocarditis due to Pasteurella is extremely rare, and there are only a few reports in the literature. Predisposing factors in the present case were alcohol abuse and reduced compliance to treatment.

CONCLUSION: Cat bites are often deep, and in rare circumstances can lead to life-threatening endocarditis. Proper surgical revision, antibiotic treatment, and patient compliance are necessary components in patient care to avoid this complication.

Place, publisher, year, edition, pages
Elsevier, 2016
Keywords
Endocarditis; Aortic valve replacement; Case report
National Category
Surgery
Research subject
Surgery esp. Thoracic and Cardivascular Surgery
Identifiers
urn:nbn:se:oru:diva-51251 (URN)10.1016/j.ijscr.2016.05.021 (DOI)000384278300025 ()27232293 (PubMedID)2-s2.0-84971255231 (Scopus ID)
Available from: 2016-07-04 Created: 2016-07-04 Last updated: 2017-11-28Bibliographically approved
Cajander, S., Tina, E., Bäckman, A., Magnuson, A., Strålin, K., Söderquist, B. & Källman, J. (2016). Quantitative Real-Time Polymerase Chain Reaction Measurement of HLA-DRA Gene Expression in Whole Blood Is Highly Reproducible and Shows Changes That Reflect Dynamic Shifts in Monocyte Surface HLA-DR Expression during the Course of Sepsis. PLoS ONE, 11(5), Article ID e0154690.
Open this publication in new window or tab >>Quantitative Real-Time Polymerase Chain Reaction Measurement of HLA-DRA Gene Expression in Whole Blood Is Highly Reproducible and Shows Changes That Reflect Dynamic Shifts in Monocyte Surface HLA-DR Expression during the Course of Sepsis
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2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 5, article id e0154690Article in journal (Refereed) Published
Abstract [en]

Introduction: A decrease in the expression of monocyte surface protein HLA-DR (mHLA-DR), measured by flow cytometry (FCM), has been suggested as a marker of immunosuppression and negative outcome in severe sepsis. However, FCM is not always available due to sample preparation that limits its use to laboratory operational hours. In this prospective study we evaluated dynamic changes in mHLA-DR expression during sepsis in relation to changes in HLA-DRA gene expression and Class II transactivator (CIITA), measured by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR).

Aims: The aims of this study were: 1. to validate the robustness of qRT-PCR measurement of HLA-DRA- and CIITA-mRNA expression, in terms of reproducibility; and 2. to see if changes in expression of these genes reflect changes in mHLA-DR expression during the course of severe and non-severe bacteraemic sepsis.

Methods and Findings: Blood samples were collected from 60 patients with bacteraemic sepsis on up to five occasions during Days 1-28 after hospital admission. We found the reproducibility of the qRT-PCR method to be high by demonstrating low threshold variations (<0.11 standard deviation (SD)) of the qRT-PCR system, low intra-assay variation of Ct-values within triplicates (≤0.15 SD) and low inter-assay variations (12%) of the calculated target gene ratios. Our results also revealed dynamic HLA-DRA expression patterns during the course of sepsis that reflected those of mHLA-DR measured by FCM. Furthermore, HLA-DRA and mHLA-DR recovery slopes in patients with non-severe sepsis differed from those in patients with severe sepsis, shown by mixed model for repeated measurements (p<0.05). However, during the first seven days of sepsis, PCR-measurements showed a higher magnitude of difference between the two sepsis groups. Mean differences (95% CI) between severe sepsis (n = 20) and non-severe sepsis (n = 40) were; on day 1-2, HLA-DRA 0.40 (0.28-0.59) p<0.001, CIITA 0.48 (0.32-0.72) p = 0.005, mHLA-DR 0.63 (0.45-1.00) p = 0.04, day 7 HLA-DRA 0.59 (0.46-0.77) p<0.001, CIITA 0.56 (0.41-0.76) p<0.001, mHLA-DR 0.81 (0.66-1.00) p = 0.28.

Conclusion: We conclude that qRT-PCR measurement of HLA-DRA expression is robust, and that this method appears to be preferable to FCM in identifying patients with severe sepsis that may benefit from immunostimulation.

Place, publisher, year, edition, pages
San Francisco, USA: Public Library of Science, 2016
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-50323 (URN)10.1371/journal.pone.0154690 (DOI)000375676400061 ()27144640 (PubMedID)
Note

Funding Agencies:

Nyckelfonden (Örebro, Sweden)

Research committee of Örebro County Council

Available from: 2016-05-27 Created: 2016-05-16 Last updated: 2018-09-18Bibliographically approved
Cajander, S., Bäckman, A., Tina, E., Strålin, K., Söderquist, B. & Källman, J. (2013). Preliminary results in quantitation of HLA-DRA by real-time PCR: a promising approach to identify immunosuppression in sepsis. Critical Care, 17(5), Article ID R223.
Open this publication in new window or tab >>Preliminary results in quantitation of HLA-DRA by real-time PCR: a promising approach to identify immunosuppression in sepsis
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2013 (English)In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 17, no 5, article id R223Article in journal (Refereed) Published
Abstract [en]

Introduction: Reduced monocyte human leukocyte antigen (mHLA)-DR surface expression in the late phase of sepsis is postulated as a general biomarker of sepsis-induced immunosuppression and an independent predictor of nosocomial infections. However, traditional monitoring of mHLA-DR by flow cytometry has disadvantages due to specific laboratory requirements. An mRNA-based HLA-DR monitoring by polymerase chain reaction (PCR) would improve the clinical usage and facilitate conduction of large multicenter studies. In this study, we evaluated an mRNA-based HLA-DR monitoring by quantitative real-time PCR (qRT-PCR) as an alternative method to traditional flow cytometry.

Methods: Fifty-nine patients with sepsis and blood culture growing pathogenic bacteria were studied. Blood samples were collected at day 1 or 2 after admission, for measurement of mHLA-DR by flow cytometry and mRNA expression of HLA-DRA and class II transactivator (CIITA) by qRT-PCR. Blood samples from blood donors were used as controls (n = 30).

Results: A significant reduced expression of mHLA-DR, HLA-DRA, and CIITA was seen in septic patients compared with controls. HLA-DRA mRNA level in whole blood was highly correlated with surface expression of mHLA-DR.

Conclusions: Patients with sepsis display a diminished expression of HLA-DR at the monocyte surface as well as in the gene expression at the mRNA level. The mRNA expression level of HLA-DRA monitored by qRT-PCR correlates highly with surface expression of HLA-DR and appears to be a possible future biomarker for evaluation of immunosuppression in sepsis.

Place, publisher, year, edition, pages
London, United Kingdom: BioMed Central, 2013
National Category
Medical and Health Sciences Clinical Laboratory Medicine
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-34293 (URN)10.1186/cc13046 (DOI)000331540900039 ()24093602 (PubMedID)2-s2.0-84884967732 (Scopus ID)
Note

Funding Agencies:

Nyckelfonden (Örebro, Sweden)

Research committee of Örebro County Council

Available from: 2014-03-13 Created: 2014-03-13 Last updated: 2018-08-29Bibliographically approved
Friberg, Ö., Dahlin, L.-G., Källman, J., Kihlström, E., Söderquist, B. & Svedjeholm, R. (2009). Collagen-gentamicin implant for prevention of sternal wound infection: long-term follow-up of effectiveness. Interactive Cardiovascular and Thoracic Surgery, 9(3), 454-458
Open this publication in new window or tab >>Collagen-gentamicin implant for prevention of sternal wound infection: long-term follow-up of effectiveness
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2009 (English)In: Interactive Cardiovascular and Thoracic Surgery, ISSN 1569-9293, E-ISSN 1569-9285, Vol. 9, no 3, p. 454-458Article in journal (Refereed) Published
Abstract [en]

In a previous randomized controlled trial (LOGIP trial) the addition of local collagen-gentamicin reduced the incidence of postoperative sternal wound infections (SWI) compared with intravenous prophylaxis only. Consequently, the technique with local gentamicin was introduced in clinical routine at the two participating centers. The aim of the present study was to re-evaluate the technique regarding the prophylactic effect against SWI and to detect potential shifts in causative microbiological agents over time. All patients in this prospective two-center study received prophylaxis with application of two collagen-gentamicin sponges between the sternal halves in addition to routine intravenous antibiotics. All patients were followed for 60 days postoperatively. From January 2007 to May 2008, 1359 patients were included. The 60-day incidences of any SWI was 3.7% and of deep SWI 1.5% (1.0% mediastinitis). Both superficial and deep SWI were significantly reduced compared with the previous control group (OR=0.34 for deep SWI, P<0.001). There was no increase in the absolute incidence of aminoglycoside resistant agents. The majority of SWI were caused by coagulase-negative staphylococci (CoNS). The incidence of deep SWI caused by Staphylococcus aureus was 0.07%. The results indicate a maintained effect of the prophylaxis over time without absolute increase in aminoglycoside resistance. (ClinicalTrials.gov NCT00484055).

Place, publisher, year, edition, pages
Amsterdam: Elsevier, 2009
National Category
Medical and Health Sciences Surgery
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-11775 (URN)10.1510/icvts.2009.207514 (DOI)19541691 (PubMedID)
Available from: 2010-09-08 Created: 2010-09-08 Last updated: 2017-12-12Bibliographically approved
Friberg, Ö., Dahlin, L.-G., Levin, L.-Å., Magnusson, A., Granfeldt, H., Källman, J. & Svedjeholm, R. (2006). Cost effectiveness of local collagen-gentamicin as prophylaxis for sternal wound infections in different risk groups. Scandinavian Cardiovascular Journal, 40(2), 117-125
Open this publication in new window or tab >>Cost effectiveness of local collagen-gentamicin as prophylaxis for sternal wound infections in different risk groups
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2006 (English)In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 40, no 2, p. 117-125Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: In a randomized trial addition of local collagen-gentamicin in the sternal wound reduced the rate of sternal wound infection (SWI) to about 50% compared to intravenous prophylaxis alone. The aim of the present study was to evaluate the economic rationale for its use in every-day clinical practice. This includes the question whether high-risk groups that may have particular benefit should be identified. DESIGN: For each patient with SWI in the trial the costs attributable to the SWI were calculated. Risk factors for SWI were identified and any heterogeneity of the effect of the prophylaxis examined. RESULTS: The mean cost of a SWI was about 14500 Euros. A cost effectiveness analysis showed that the prophylaxis was cost saving. The positive net balance was even higher in risk groups. Assignment to the control group, overweight, diabetes, younger age, mammarian artery use, left ventricular ejection fraction <35% and longer operation time were independent risk factors for infection. CONCLUSION: The addition of local collagen-gentamicin to intravenous antibiotic prophylaxis was dominant, i.e. resulted in both lower costs and fewer wound infections.

National Category
Medical and Health Sciences Infectious Medicine Surgery
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-12045 (URN)10.1080/14017430500363024 (DOI)16608782 (PubMedID)
Available from: 2010-10-05 Created: 2010-10-05 Last updated: 2017-12-12Bibliographically approved
Friberg, Ö., Dahlin, L.-G., Söderquist, B., Källman, J. & Svedjeholm, R. (2006). Influence of more than six sternal fixation wires on the incidence of deep sternal wound infection. The thoracic and cardiovascular surgeon, 54(7), 468-473
Open this publication in new window or tab >>Influence of more than six sternal fixation wires on the incidence of deep sternal wound infection
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2006 (English)In: The thoracic and cardiovascular surgeon, ISSN 0171-6425, E-ISSN 1439-1902, Vol. 54, no 7, p. 468-473Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The aim of the present study was to examine the influence of the number of sternal fixation wires used on deep sternal wound infection rate and to analyze any possible interaction between this and local collagen-gentamicin prophylaxis evaluated in a previous trial. METHODS: The number of sternal fixation wires in all patients from one of two participating centers was counted. The patients were categorized according to six or fewer (standard technique, ST group) vs. seven or more wires (extra wires, XW group). RESULTS: The incidence of deep sternal wound infection was 4.2 % in the ST group and 0.4 % in the XW group ( P = 0.001). An analysis of the effect of local gentamicin, excluding the ST group from the analysis, showed an approximately 70 % reduction in sternal wound infection for all depths. CONCLUSION: This study supports the theory that additional fixation wires at the lower sternum actually reduce the incidence of deep wound infections. We suggest that a rigid sternal fixation is required to achieve the full benefit of local collagen-gentamicin prophylaxis.

National Category
Medical and Health Sciences Surgery
Research subject
Surgery esp. Thoracic and Cardivascular Surgery
Identifiers
urn:nbn:se:oru:diva-11121 (URN)10.1055/s-2006-924437 (DOI)17089314 (PubMedID)
Available from: 2010-06-16 Created: 2010-06-16 Last updated: 2017-12-12Bibliographically approved
Söderquist, B., Alriksson, I., Källman, J. & Kihlström, E. (2006). The influence of adhesive and invasive properties of Staphylococcus aureus defective in fibronectin-binding proteins on secretion of interleukin-6 by human endothelial cells. Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), 114(2), 112-116
Open this publication in new window or tab >>The influence of adhesive and invasive properties of Staphylococcus aureus defective in fibronectin-binding proteins on secretion of interleukin-6 by human endothelial cells
2006 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 114, no 2, p. 112-116Article in journal (Refereed) Published
Abstract [en]

Fibronectin-binding proteins (FnBP) are surface adhesins of Staphylococcus aureus documented to be virulence attributes in, for example, endovascular infections. By using mutants of S. aureus defective in the FnBPA and B genes we have investigated whether these adhesins affect cytokine expression in human umbilical vein endothelial cells (HUVEC). S. aureus expressing FnBPA and B adhered to and were internalized into HUVEC to a greater extent compared to mutants defective in expression of FnBP. Production and release of IL-6 was higher from endothelial cells infected with the parent FnBP-expressing strain compared to the FnBP-defective mutants. These results indicate that adhesion to and invasion of S. aureus into endothelial cells are important regulators of cytokine expression.

National Category
Medical and Health Sciences Infectious Medicine
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-12046 (URN)10.1111/j.1600-0463.2006.apm_319.x (DOI)16519747 (PubMedID)
Available from: 2010-10-05 Created: 2010-10-05 Last updated: 2017-12-12Bibliographically approved
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