Mannose-Binding Lectin Binds to a Range of Clinically Relevant Microorganisms and Promotes Complement Deposition

Neth, Olaf; Jack, Dominic; Dodds, Alister W.; Holzel, Helen; Klein, Nigel; Turner, Malcolm

doi:10.1128/iai.68.2.688-693.2000

Cited by 516 publications

(415 citation statements)

References 37 publications

(40 reference statements)

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“…6 MBL is a patternrecognition receptor that binds to surface carbohydrates on microorganisms, which in turn activates the complement system. 7,8 MBL binds to a range of respiratory pathogens associated with COPD exacerbations, including Haemophilus influenzae and influenza A virus. 7,8 Single nucleotide polymorphisms in the coding and promoter regions of the MBL gene (MBL2) are known to have functional effects on serum MBL levels.…”

Section: Introductionmentioning

confidence: 99%

“…7,8 MBL binds to a range of respiratory pathogens associated with COPD exacerbations, including Haemophilus influenzae and influenza A virus. 7,8 Single nucleotide polymorphisms in the coding and promoter regions of the MBL gene (MBL2) are known to have functional effects on serum MBL levels. 9,10 Low-producing MBL2 polymorphisms have been associated with frequency of respiratory tract infections in children, 11 earlier onset of infection, particularly pneumonia, in adults with systemic lupus erythematosus, 12 and higher risk of invasive pneumococcal disease.…”

Section: Introductionmentioning

confidence: 99%

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Mannose-binding lectin gene polymorphism predicts hospital admissions for COPD infections

et al. 2003

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Infection frequently causes exacerbations of chronic obstructive pulmonary disease (COPD). Mannose-binding lectin (MBL) is a pattern-recognition receptor that assists in clearing microorganisms. Polymorphisms in the MBL2 gene reduce serum MBL levels and are associated with risk of infection. We studied whether the MBL2 codon 54 B allele affected serum MBL levels, admissions for infective exacerbation in COPD and disease susceptibility. Polymorphism frequency was determined by PCR-RFLP in 200 COPD patients and 104 smokers with normal lung function. Serum MBL was measured as mannan-binding activity in a subgroup of 82 stable COPD patients. Frequency of COPD admissions for infective exacerbation was ascertained for a 2-year period. The MBL2 codon 54 B allele reduced serum MBL in COPD patients. In keeping, patients carrying the low MBL-producing B allele had increased risk of admission for infective exacerbation (OR 4.9, P corrected ¼ 0.011). No association of MBL2 genotype with susceptibility to COPD was detected. In COPD, serum MBL is regulated by polymorphism at codon 54 in its encoding gene. Low MBL-producing genotypes were associated with more frequent admissions to hospital with respiratory infection, suggesting that the MBL2 gene is disease-modifying in COPD. MBL2 genotype should be explored prospectively as a prognostic marker for infection risk in COPD.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mannose-binding lectin gene polymorphism predicts hospital admissions for COPD infections

et al. 2003

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“…First, in vitro studies show that S. pneumoniae does not have a strong binding affinity for MBL 7. In addition, the immune system has several other, maybe more effective, ways to eliminate S. pneumoniae 13, 35, 36.…”

Section: Discussionmentioning

confidence: 99%

“…In addition MBL opsonizes micro‐organisms, thereby promoting phagocytosis. Deficiency of MBL may increase the risk of infection in adults because of impaired phagocytosis by polymorphonuclear leucocytes secondary to defective opsonization and by lack of complement‐mediated lysis 6, 7, 8, 9. The level of MBL and its functionality is mainly regulated by three single nucleotide polymorphisms (SNPs) in exon 1 and one SNP in the promoter region of the MBL gene ( MBL2 ).…”

Section: Introductionmentioning

confidence: 99%

Mannose‐binding lectin and l‐ficolin polymorphisms in patients with community‐acquired pneumonia caused by intracellular pathogens

et al. 2017

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SummaryCommunity‐acquired pneumonia (CAP) is the leading infectious disease requiring hospitalization in the western world. Genetic variability affecting the host response to infection may play a role in susceptibility and outcome in patients with CAP. Mannose‐binding lectin (MBL) and l‐ficolin (l‐FCN) are two important activators of the complement system and they can enhance phagocytosis by opsonization. In a prospective cohort of 505 Dutch patients with CAP and 227 control participants we studied whether polymorphisms in the MBL (MBL2) and FCN (FCN2) genes influenced susceptibility and outcome. No difference in frequency of these genotypes was found between patients with CAP in general and controls. However, the +6424G>T single nucleotide polymorphism (SNP) in FCN2 was more common in patients with a Coxiella burnetii pneumonia (P = 0·014). Moreover, the haplotypes coding for the highest MBL serum levels (YA/YA and YA/XA) predisposed to atypical pneumonia (C. burnetii, Legionella or Chlamydia species or Mycoplasma pneumoniae) compared with controls (P = 0·016). Furthermore, patients with these haplotypes were more often bacteraemic (P = 0·019). It can therefore be concluded that MBL2 and FCN2 polymorphisms are not major risk factors for CAP in general, but that the +6424G>T SNP in the FCN2 gene predisposes to C. burnetii pneumonia. In addition, patients with genotypes corresponding with high serum MBL levels are at risk for atypical pneumonia, possibly caused by enhanced phagocytosis, thereby promoting cell entry of these intracellular bacteria.

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“…MBL binding to the bacteria was assayed by a direct immunofluorescence method with flow cytometric detection [18,19]. Briefly, bacteria were suspended in veronal buffered saline supplemented with 5 mm CaCl 2 (VBS 1 ) at an A 540 of 1.…”

Section: Detection Of Mbl Bindingmentioning

confidence: 99%

Differential recognition of obligate anaerobic bacteria by human mannose-binding lectin

Townsend

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Turner

et al. 2001

Clinical and Experimental Immunology

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SUMMARYDeficiency of the innate, humoral immune component mannose-binding lectin (MBL) predisposes individuals to a variety of infections, but the importance of MBL in infection by anaerobes has not been addressed. The attachment of MBL to a wide range of anaerobic bacteria associated with human disease and colonization was surveyed. The results suggest that for the species we examined, resistance to MBL binding may be associated with organisms that are more commonly pathogenic and that MBL binding to some bacteria may be phase variable.

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Mannose-Binding Lectin Binds to a Range of Clinically Relevant Microorganisms and Promotes Complement Deposition

Cited by 516 publications

References 37 publications

Mannose-binding lectin gene polymorphism predicts hospital admissions for COPD infections

Mannose-binding lectin gene polymorphism predicts hospital admissions for COPD infections

Mannose‐binding lectin and l‐ficolin polymorphisms in patients with community‐acquired pneumonia caused by intracellular pathogens

Differential recognition of obligate anaerobic bacteria by human mannose-binding lectin

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