MBL-associated serine proteases (MASPs) and infectious diseases

Abstract

The lectin pathway of the complement system has a pivotal role in the defense against infectious organisms. After binding of mannan-binding lectin (MBL), ficolins or collectin 11 to carbohydrates or acetylated residues on pathogen surfaces, dimers of MBL-associated serine proteases 1 and 2 (MASP-1 and MASP-2) activate a proteolytic cascade, which culminates in the formation of the membrane attack complex and pathogen lysis. Alternative splicing of the pre-mRNA encoding MASP-1 results in two other products, MASP-3 and MAp44, which regulate activation of the cascade. A similar mechanism allows the gene encoding MASP-2 to produce the truncated MAp19 protein. Polymorphisms in MASP1 and MASP2 genes are associated with protein serum levels and functional activity. Since the first report of a MASP deficiency in 2003, deficiencies in lectin pathway proteins have been associated with recurrent infections and several polymorphisms were associated with the susceptibility or protection to infectious diseases. In this review, we summarize the findings on the role of MASP polymorphisms and serum levels in bacterial, viral and protozoan infectious diseases.

Genetically regulated hepatic transcripts and pathways orchestrate haematological, biochemical and body composition traits

“…MASP2 encodes a member of the peptidase S1 family of serine proteases and cleaves complement components C2 and C4 to generate C3 convertase in the lectin pathway of the complement system. Polymorphisms in MASP2 genes are associated with protein serum levels and functional activity and with susceptibility to or protection against infectious diseases65. Significantly higher MASP2 levels are found in children and adults with type 1 diabetes mellitus66.…”

Identification of polymorphisms in the bovine collagenous lectins and their association with infectious diseases in cattle

“…As with human MASP1 , the transcript and predicted transcripts that encode the three MASP1 isoforms share the first 8 exons; thus, the cluster of variants noted in intron 2 is also present in intron 2 for all of these predicted transcripts. Genetic mutations resulting in human MASP1 deficiency are associated with infectious disease, and several intronic mutations leading to MASP1 deficiency have been identified, though none are identical to the associations found here (Ingels et al 2013; Beltrame et al 2015). Again, the relative similarity of the allele frequencies for the different loci suggests significant linkage disequilibrium.…”

“…Again, the relative similarity of the allele frequencies for the different loci suggests significant linkage disequilibrium. It should be noted that mutations that inhibit the function of the MASPs (and complement-activating collagenous lectins) may also confer benefits: excess activation of complement can contribute to tissue damage or autoimmune disease, and decreased or more moderate levels of complement activity may therefore be beneficial in some scenarios (Beltrame et al 2015). …”

Collectin Kidney 1 Plays an Important Role in Innate Immunity against <b><i>Streptococcus pneumoniae</i></b> Infection

“…Among these biological functions, complement activation is considered to be particularly important in protecting the body from infectious diseases [25,26] . Furthermore, it was found that complement factors were present in the lung which might activate complement system during bacterial infection [25,27] .…”

“…6 a). It is well known that microbes opsonized by complement are easily recognized by phagocytes, which express complement receptors on their surface, and consequently lead to increased phagocytosis [26] . In in vitro analysis, rhCL-K1 could increase phagocytosis of E. coli , but it did not enhance the phagocytosis of S. pneumoniae ( Fig.…”