The Role of Human Genetics in HIV-1 Infection
Thomas R. O’Brien in Chemokine Receptors and AIDS, 2019
Mannose-binding lectin (MBL) is a member of the collectin family of proteins and is an important constituent of the innate immune system (180–182). MBL activates complement (183) and acts in the first line of defense against various bacterial, viral, and parasitic infections, before the establishment of adaptive immune protection by B and T cells (180). Low serum levels of MBL are associated with opsonization defects and impaired phagocytosis (184–186). The MBL gene is located on chromosome 10q (187,188), and polymorphisms in the first exon have been shown to be important in determining the level of circulating MBL (189,190). Single amino acid variants associated with lower MBL serum concentrations include G→D at codon 54 (allele B) (191), G→E at codon 57 (allele C) (189), and R→C at codon 52 (allele D) (190). Polymorphisms in the promoter region of the MBL gene have also been shown to affect serum concentration of MBL (192).
The complement system in health and disease
Gabriel Virella in Medical Immunology, 2019
The lectin pathway is initiated by target recognition through the binding of circulating lectins, such as plasma mannan-binding lectin (MBL) and Ficolins 1–3. These protein components belong to the collectin family, structurally resemble C1q, and are involved with the recognition of foreign organisms such as bacteria and virus. Mannan, a constituent of the polysaccharide capsules of many pathogenic fungi and yeasts (e.g., Cryptococcus neoformans and Candida albicans), is one of several polysaccharide substances to which MBL binds via Ca2+-dependent interactions, while bacterial lipoteichoic acid and peptidoglycan associate with serum Ficolins. In addition to carbohydrate motifs of microorganisms, MBL can bind to glycoproteins on the envelope of several types of viruses. The activation of the lectin pathway does not involve antigen-antibody interactions. Like the alternative complement pathway, the lectin pathway is an innate system designed to activate the complement system independently of specific antibodies, and as such requires no adaptive immune system help. Both mannan-binding lectin and ficolins are acute-phase reactants, meaning that their concentration increases during infection and inflammation. Both types of lectins stay associated with serum serine proteases, and upon binding initiation proceeds through the activations of processes mediated by MBL-associated serine proteases (MASPs) such as MASP-1, MASP-2, and MASP-3. These proteases form a tetrameric complex similar to the one formed by C1r and C1s of the classical pathway, and MASP-2 subsequently cleaves C4 and C2, and then subsequently C3 in the same manner as that of the classical pathway (Figure 9.3).
Overview of lung surfactant and respiratory distress syndrome
Anthony J. Hickey, Heidi M. Mansour in Inhalation Aerosols, 2019
SP-A is the most abundant of the four surfactant proteins and is an important mediator of innate and adaptive immunity in the lung. In humans, SP-A is comprised of gene products from SFTPA1 (SP-A1) and SFTPA2 (SP-A2) that oligomerize into six trimeric subunits to form an octadecomer (11). As a member of the collectin family of proteins, SP-A contains a collagen-like domain and highly conserved carbohydrate recognition domain (CRD). The CRD enables SP-A to bind to components of bacterial cell walls, thereby enhancing their uptake by resident macrophages.
Simulation of respiratory tract lining fluid for in vitro dissolution study
Published in Expert Opinion on Drug Delivery, 2021
Rakesh Bastola, Paul M. Young, Shyamal C. Das
Lung surfactant (LS) is a surface-active lipid–protein material [32]. Around 92% of LS is lipid and 8% is surfactant protein (SP) by mass [33]. Lipids include fully saturated dipalmitoylphosphatidylcholine (DPPC) as the major phospholipid. In addition, LS contains unsaturated phosphatidylcholine (PC), anionic phosphatidylglycerol (PG) and phosphatidylinositol (PI) as well as neutral lipids such as cholesterol (also being the most prominent) [33]. Around 8% of the total LS mass contains four specific SPs, and they are categorized into two groups. The larger hydrophilic surfactant protein A (SP-A) and surfactant protein D (SP-D) come under the collectin protein family. They are basically responsible for innate immunity. The smaller hydrophobic surfactant protein B (SP-B) and surfactant protein C (SP-C) are inserted in and between the LS-associated phospholipid layers. They are necessary for LS interfacial adsorption and are responsible for the safeguarding of surfactant film stability during consecutive breathing cycles [33].
Mannose-Binding Lectin Levels in Late-Onset Sepsis in Preterm Infants: Results from a Prospective Study in a Tertiary Care Center
Published in Fetal and Pediatric Pathology, 2020
Pelin Dogan, Hilal Ozkan, Nilgun Koksal, Haluk Barbaros Oral, Solmaz Celebi, Onur Bagci, Ipek Guney Varal
Mannose-binding lectin (MBL) is a member of the collectin family that enables the lectin pathway of the complement system, and it has an important role in binding to several microorganisms. Common polymorphisms occur at the MBL2 locus, leading to decreased circulating MBL levels. MBL deficiency is observed in approximately one-third of the population. Low MBL levels are associated with increased infection rates in preterm infants [5]. The adaptive host response to infection in preterm infants is damaged for miscellaneous reasons. The absence of passively derived maternal antibodies, decreased function of neutrophils and suboptimal functioning of the acquired immune system might be liable for the host-defence disruptions in infants; hence, newborns have increased sensitivity to infections [6]. MBL is considered an important part of the innate immune system, and its deficiency may be a risk factor for infection in this patient category [7, 8].
Importance of mannose-binding lectin2 polymorphism (rs1800450) in infections in children
Published in Biomarkers, 2022
Metin Uysalol, Suheyla Gumus, Raif Yildiz, Ezgi Pasli Uysalol, Sacide Pehlivan, Mustafa Pehlivan, Istemi Serin
Mannose-binding lectin (MBL) is a serine protease belonging to the collectin family and is believed to be an important factor in the inherited immune system. MBL binds to the surface of a wide range of microorganisms by its ability to recognise, function either directly as an opsonin or through activation of the complement system, thus increasing the phagocytosis of microorganisms by macrophages and neutrophils (Jacobson et al.2020). There are several known mutations in the MBL2 gene and promoter regions located on the long arm of chromosome 10, resulting in a large number of haplotypes. This genetic polymorphism is associated with different levels of MBL expression and activity (Best et al.2009, Jacobson et al.2020). Studies are showing that genotypes associated with low MBL levels may predispose to certain forms of infection or impaired immune response, particularly in neonates as well as adults (Best et al.2009, Jacobson et al.2020). Several studies on the association of MBL genetic polymorphism and/or MBL plasma levels with severe infections, sepsis, and septic shock have shown an increased risk of developing sepsis in patients with MBL deficiency (Eisen et al.2003, Best et al.2009). In our study, we aimed to reveal the distribution of different MBL genotypes in patients diagnosed with acute bronchiolitis and pneumonia.
Related Knowledge Centers
- Inflammation
- Innate Immune System
- Lectin
- Opsonin
- Pattern Recognition Receptor
- Platelet
- Phagocytosis
- Pathogen-Associated Molecular Pattern
- Damage-Associated Molecular Pattern
- Complement System