Mannose-Binding Lectin Deficiency and Respiratory Tract Infection

Abstract

Mannose-binding lectin (MBL) is an innate immune system pattern recognition protein that kills a wide range of pathogenic microbes through complement activation. A substantial proportion of all human populations studied to date have MBL deficiency due to MBL2 polymorphisms, which potentially increases susceptibility to infectious disease. MBL binds numerous respiratory pathogens but the capsule of Streptococcus pneumoniae abrogates its efficient binding. Clinical studies in humans have shown that MBL deficiency appears to predispose to severe respiratory tract infection. A recent meta-analysis shows that MBL deficiency was associated with death in patients with pneumococcal infection after adjusting for bacteraemia and comorbidities. Human clinical studies have also shown associations between MBL deficiency and various less common respiratory infections. Intracellular infections like tuberculosis may be less common with MBL deficiency because of reduced opsonophagocytosis. Lung secretions contain small amounts of MBL that are potentially sufficient to activate complement, but their measurement is confounded by dilution inherent in collection techniques. Therefore, if this protein does play a role in pulmonary immunity it is presumably through prevention of haematogenous dissemination of respiratory pathogens while adding to mucosal defences. Ficolins are collectins that are structurally and functionally related to MBL and are either present in serum or expressed in tissues including the lung. Limited variation in serum levels of L- and H-ficolin result from the presence of FCN2 and FCN3 polymorphisms. Initial studies on the impact of FCN2 polymorphisms or low L-ficolin levels do not seem to show major associations with respiratory infection. MBL is being developed as a new immunotherapeutic agent for prevention of infection in immunocompromised hosts. The available literature suggests that it may also be of benefit in MBL deficient patients with severe pneumonia. This review concentrates on clinical associations between MBL deficiency and susceptibility to respiratory tract infection.

The Deficiency of Serum Mannose Binding Lectin in Early Onset Idiopathic Pulmonary Fibrosis and Familial Cases

“…Common pathogens include Pneumocystitis jiroveci, Staplococcus, Streptococcus, HIV, Candida, Chlamydia, Meningococcus and Influenza virus [18][19][20].…”

“…Within the alveoli MBL has 4 main actions [18,21]. It promotes opsonisation and phagocytosis of micro-organisms.…”

The Role of Nanometer-Scaled Ligand Patterns in Polyvalent Binding by Large Mannan-Binding Lectin Oligomers

“…Mannan-binding lectin (MBL; also known as mannose-binding lectin, mannan-or mannose-binding protein) constitutes a part of the body's protection against infection, as demonstrated by several clinical studies, as well as experimental evidence from animal models focusing on the protective effect in various viral and bacterial infections (4)(5)(6). Binding of MBL to microbial patterns activates the complement system, which leads to the deposition of other plasma proteins, notably fragments of complement factor C3, facilitating uptake of microbial agents by leukocytes or direct lysis of membrane-enveloped micro-organisms (1).…”

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

“…In recent years, the association between genetic variations in MBL2 , and to a lesser extent FCN2 , and susceptibility to disease have been the subject of various studies 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31. An association between MBL2 polymorphisms and clinical outcome has been described in children with recurrent infections22 and in adult patients with meningococcal sepsis 17…”

“…An association between MBL2 polymorphisms and clinical outcome has been described in children with recurrent infections22 and in adult patients with meningococcal sepsis 1729 Behçet's disease,20 peritonitis in patients undergoing peritoneal dialysis28 and recurrent respiratory infections in children 16, 18.…”