Mannan-binding lectin-associated serine protease-2 (MASP-2) deficiency in two patients with pulmonary tuberculosis and one healthy control

Sokołowska, Anna; Szala, Agnieszka; Świerzko, Anna St.; Kozińska, Monika; Niemiec, Tomasz; Błachnio, Maria; Augustynowicz–Kopeć, Ewa; Dziadek, Jarosław; Cedzyński, Maciej

doi:10.1038/cmi.2014.19

Cited by 25 publications

(20 citation statements)

References 11 publications

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“…In addition, ficolin-2 has been found to recognize ManLAM and protect against a virulent M. tuberculosis strain both in vitro and in vivo . MASP-2 deficiency caused by homozygosity for the p.120G amino acid substitution was also recently reported in two persons with pulmonary tuberculosis (Sokolowska et al, 2015). MASP2 SNPs with a possible regulatory role in gene expression have been further associated with susceptibility to the disease, e.g.…”

Section: Tuberculosismentioning

confidence: 75%

MBL-associated serine proteases (MASPs) and infectious diseases

Beltrame

Boldt

Catarino

et al. 2015

Molecular Immunology

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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.

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Section: Tuberculosismentioning

confidence: 75%

MBL-associated serine proteases (MASPs) and infectious diseases

Beltrame

Boldt

Catarino

et al. 2015

Molecular Immunology

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“…Reports on genetic defects in the MASP1 and MASP2 are rare. MASP‐2 defects have been suggested to be associated with various infectious diseases, but cases are rare and the clinical penetrance is debatable . However, newly described MASP1 mutations that affect a site on the common heavy chain of MAP‐1, MASP‐1 and ‐3, and several sites in the serine protease domain of MASP‐3 seem to be a cause of the rare autosomal‐recessive development 3MC syndrome .…”

Section: The Masp Familymentioning

confidence: 99%

A journey through the lectin pathway of complement—MBL and beyond

Garred

Genster

Pilely

et al. 2016

Immunological Reviews

337

302

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Mannose-binding lectin (MBL), collectin-10, collectin-11, and the ficolins (ficolin-1, ficolin-2, and ficolin-3) are soluble pattern recognition molecules in the lectin complement pathway. These proteins act as mediators of host defense and participate in maintenance of tissue homeostasis. They bind to conserved pathogen-specific structures and altered self-antigens and form complexes with the pentraxins to modulate innate immune functions. All molecules exhibit distinct expression in different tissue compartments, but all are found to a varying degree in the circulation. A common feature of these molecules is their ability to interact with a set of serine proteases named MASPs (MASP-1, MASP-2, and MASP-3). MASP-1 and -2 trigger the activation of the lectin pathway and MASP-3 may be involved in the activation of the alternative pathway of complement. Furthermore, MASPs mediate processes related to coagulation, bradykinin release, and endothelial and platelet activation. Variant alleles affecting expression and structure of the proteins have been associated with a variety of infectious and non-infectious diseases, most commonly as disease modifiers. Notably, the severe 3MC (Malpuech, Michels, Mingarelli, and Carnevale) embryonic development syndrome originates from rare mutations affecting either collectin-11 or MASP-3, indicating a broader functionality of the complement system than previously anticipated. This review summarizes the characteristics of the molecules in the lectin pathway.

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“…Variants in MASP2 leading to functional deficiencies have been reported [41,42] but their association with diseases so far have been subject of controversy [41,[43][44][45][46][47]. In humans, relatively common polymorphisms within genes involved in the lectin pathway were associated with infectious and autoimmune diseases [43,[48][49][50][51].…”

Section: Discussionmentioning

confidence: 99%

Herpes simplex encephalitis in adult patients with MASP-2 deficiency

et al. 2019

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We report here two cases of Herpes simplex virus encephalitis (HSE) in adult patients with very rare, previously uncharacterized, non synonymous heterozygous G634R and R203W substitution in mannan-binding lectin serine protease 2 (MASP2), a gene encoding a key protease of the lectin pathway of the complement system. None of the 2 patients had variants in genes involved in the TLR3-interferon signaling pathway. Both MASP2 variants induced functional defects in vitro, including a reduced (R203W) or abolished (G634R) protein secretion, a lost capability to cleave MASP-2 precursor into its active form (G634R) and an in vivo reduced antiviral activity (G634R). In a murine model of HSE, animals deficient in mannose binding lectins (MBL, the main pattern recognition molecule associated with MASP-2) had a decreased survival rate and an increased brain burden of HSV-1 compared to WT C57BL/6J mice. Altogether, these data suggest that MASP-2 deficiency can increase susceptibility to adult HSE. Author summaryHuman herpes virus type 1 (HSV-1) infects a large number of individuals during their life, with manifestations usually limited to mild and self-limiting inflammation of the oral mucosa (cold sore). However, HSV-1 can cause a very severe disease of the brain called Herpes simplex encephalitis (HSE) in 1 out of 250'000-500'000 individuals per year. The reasons why HSV-1 can cause such a devastating disease in a very limited number of individuals are unknown. Increasing evidence suggests that susceptibility to HSE in children can results from genetic variations in the immune system, in particular in a viral detection PLOS Pathogens | https://doi.pathway called the Toll-like receptor 3 (TLR3)-interferon (IFN) axis. Fewer data are available to explain HSE in adult patients. Here, we describe two adult patients with HSE who carry mutations in a gene called mannan-binding lectin serine protease 2 (MASP2), which is part of an immune pathway different from the TLR3-IFN axis, called the lectin pathway of the complement system. We demonstrate that MASP2 mutations induce functional defects in immune defense against HSV-1 that prevent viral replication. Mice deficient in the lectin pathway have higher mortality compared to wild-type mice after HSV-1 infection. Altogether, our study suggests that susceptibility to HSE in adults relies of immune deficiencies that are different from those causing HSE in children.Herpes simplex encephalitis and MASP-2 deficiency PLOS Pathogens | https://doi.

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Mannan-binding lectin-associated serine protease-2 (MASP-2) deficiency in two patients with pulmonary tuberculosis and one healthy control

Cited by 25 publications

References 11 publications

MBL-associated serine proteases (MASPs) and infectious diseases

MBL-associated serine proteases (MASPs) and infectious diseases

A journey through the lectin pathway of complement—MBL and beyond

Herpes simplex encephalitis in adult patients with MASP-2 deficiency

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