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The ambiguous role of mannose-binding lectin (MBL) in human immunity.

ABSTRACT: Mannose-binding lectin (MBL) and lectin complement pathway have become targets of increasing clinical interest. Many aspects of MBL have been recently explored, including the structural properties that allow it to distinguish self from non-self/altered-self structures. Experimental evidences have declared the additional 5'- and 3'-variants that in amalgamation with well-known secretor polymorphisms change MBL function and concentration. Moreover, the current review highlights the differential behavior of MBL on exposure with extra/intracellular pathogens and in autoimmune diseases, stressing the fact that "high MBL levels can increase diseases susceptibility," a paradox that needs justification. Attributable to these discrepancies, no absolute level of MBL deficiency could be defined so far and thus must be interpreted for specific diseases through case-control population-specific designs. Overall, it is evident that further research is needed about MBL and the lectin pathway of complement. Particularly, the transformative role of MBL over evolution is of interest and its role with regard to pathogenesis of different diseases and potential therapeutic targets within the respective pathways should be further explored. Apart from this, it is necessary to adopt an extensive locus-wide methodology to apprehend the clinical significance of MBL2 polymorphisms in a variety of infectious diseases by the future studies.

SUBMITTER: Kalia N

PROVIDER: S-EPMC7917369 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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The ambiguous role of mannose-binding lectin (MBL) in human immunity.

Kalia Namarta N Singh Jatinder J Kaur Manpreet M

Open medicine (Warsaw, Poland) 20210217 1

Mannose-binding lectin (MBL) and lectin complement pathway have become targets of increasing clinical interest. Many aspects of MBL have been recently explored, including the structural properties that allow it to distinguish self from non-self/altered-self structures. Experimental evidences have declared the additional 5'- and 3'-variants that in amalgamation with well-known secretor polymorphisms change MBL function and concentration. Moreover, the current review highlights the differential be ...[more]

PMID: 33681468

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Project description:ObjectivesCutaneous ischemia/reperfusion (CI/R) injury has shown to play a significant role in chronic wounds such as decubitus ulcers, diabetic foot ulcers, atherosclerotic lesions, and venous stasis wounds. CI/R also plays a role in free tissue transfer in reconstructive microsurgery and has been linked to clinical burn-depth progression after thermal injury. While the role of the complement system has been elucidated in multiple organ systems, evidence is lacking with respect to its role in the skin. Therefore, we evaluated the role of the complement system in CI/R injury.MethodsUsing a single pedicle skin flap mouse model of acute CI/R, we performed CI/R in wild-type (WT) mice and complement knock out (KO) mice, deficient in either C1q (C1q KO; classical pathway inhibition), mannose-binding lectin (MBL null; lectin pathway inhibition) or factor B (H2Bf KO; alternative pathway inhibition). Following 10 h ischemia and 7 days reperfusion, mice were sacrificed, flaps harvested and flap viability assessed via Image J software. The flap necrotic area was expressed as % total flap area. In another group, mice were sacrificed following CI/R with 10 h ischemia and 48 h reperfusion. Two cranial skin flap samples were taken for gene expression analysis of IL1b, IL6, TNFα, ICAM1, VCAM1, IL10, IL13 using real-time polymerase chain reaction (RT-PCR).ResultsFollowing CI/R, MBL null mice had a statistically significant smaller %necrotic flap area compared to WT mice (10.6 vs. 43.1%; p<0.05) suggesting protection from CI/R. A significantly reduced mean %necrotic flap area was not seen in either C1q KO or H2Bf KO mice relative to WT (22.9 and 31.3 vs. 43.1%; p=0.08 and p=0.244, respectively). There were no statistically significant differences between groups for markers of inflammation (TNFα, ICAM1, VCAM1, IL1b, IL6). In contrast, mRNA levels of IL10, a regulator of inflammation, were significantly increased in the MBL null group (p=0.047).ConclusionsWe demonstrated for the first time a significant role of MBL and the lectin complement pathway in ischemia/reperfusion injury of the skin and a potential role for IL10 in attenuating CI/R injury, as IL10 levels were significantly increased in the tissue from the CI/R-protected MBL null group.

Project description:ObjectiveTuberculosis (TB) is caused by infection of Mycobacterium tuberculosis. Host genetic variability is an important determinant of the risk of developing TB in humans. Although the association between MBL polymorphisms and TB has been studied in various populations, the results are controversial. The aim of this study was to investigate mannose-binding lectin (MBL) gene polymorphisms with susceptibility to pulmonary tuberculosis (PTB) in a Lur population of Iran.MethodsIn this case-control study, four functional MBL gene polymorphisms (HL, XY, PQ and AB) were genotyped by using PCR Single Strand Conformation Polymorphism (SSCP) technique in a Lur population living in Lorestan Province, consisting of 100 patients with pulmonary tuberculosis (PTB) age and sex matched 100 healthy controls (HCs). Association analyses were performed with the SPSS 21 statistical software.ResultsWe found that MBL (HH) genotype polymorphism significantly was associated with increased susceptibility to TB (35% in patients vs. 22% in controls, P = 0.0417, OR = 1.909, %95 CI = 1.020-3.573). Additionally, H allele showed a significant association with increased risk of TB (56.5% in patients vs. 46% in controls, P = 0.0357, OR = 1.525, %95 CI = 1.028-2.262). Also, the distribution of L allele in patients was significantly lower frequency in TB patients compared to controls (43.5% vs. 54%, P = 0.0357, OR = 0.656, %95 CI = 0.442-0.973). However, the allelic and genotypic frequencies of AB, XY and PQ polymorphisms were not significantly different between the patients and the controls. We couldn't detect any significant differences between haplotypes among TB patients and healthy controls.ConclusionsOur findings demonstrated that HH genotype and H allele may increase the susceptibility to pulmonary TB in the Lur population of Iran, although L allele may decrease the susceptibility to pulmonary TB in this population. We suggest that it is necessary to further more studies with larger sample size and other ethnic population.

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The ambiguous role of mannose-binding lectin (MBL) in human immunity.

Publications

The ambiguous role of mannose-binding lectin (MBL) in human immunity.

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