Mannan-binding lectin deficiency in pediatric patients with inflammatory bowel disease

Bąk‐Romaniszyn, Leokadia; Szala, Agnieszka; Sokołowska, Anna; Mierzwa, Grażyna; Czerwionka-Szaflarska, Mieczysława; Świerzko, Anna St.; Zeman, Krzysztof; Cedzyński, Maciej

doi:10.3109/00365521.2011.594087

Cited by 26 publications

(15 citation statements)

References 8 publications

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“…Of note, there is clinical and experimental evidence to support the role of MBL in limiting pathogen-induced mucosal damage. Although not without controversy, there are reports that MBL deficiency or low MBL levels are associated with IBD, at least in certain populations (26-28). It has also been shown that in a DSS-induced colitis model, MBL deficiency results in exacerbated colitis in response to normally mild gut pathogens (29).…”

Section: Discussionmentioning

confidence: 99%

Complement-Dependent Injury and Protection in a Murine Model of Acute Dextran Sulfate Sodium-Induced Colitis

Schepp-Berglind

Atkinson

Elvington

et al. 2012

The Journal of Immunology

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Complement plays a key role in the pathophysiology of many inflammatory diseases, and here we investigated the role of complement in the pathogenesis of inflammatory bowel disease (IBD). Compared to wild type (wt) mice, mice deficient in C3 or factor B (fB) were protected from acute DSS-induced colitis. C1q/MBL double deficient mice, however, exhibited more severe colitis than wt mice. When mice were allowed to recover after DSS treatment, all C1q/MBL-/- mice died by day 2 of recovery period and, surprisingly, all C3-/- and fB-/- mice died by day 5. Serum endotoxin levels were significantly increased in complement deficient mice prior to death, particularly in C1q/MBL-/- mice, and antibiotic treatment prevented the lethal effect of DSS in all complement deficient mice. In contrast to complement deficiency, targeted complement inhibition with either CR2-Crry (blocks all pathways at C3 activation) or CR2-fH (blocks alternative pathway), was highly protective at treating established acute colitis. Endotoxin levels remained low in complement inhibited mice, and complement inhibition also reduced inflammatory cytokines, leuckocyte infiltration and tissue injury, while improving wound repair and mucosal healing. CR2-fH provided more effective protection than CR2-Crry. Thus, complement has both pathogenic and protective roles in acute DSS-induced colitis, and whereas the alternative pathway appears to play a key role in tissue inflammation and injury, the classical/lectin pathway provides important protection in terms of host defense and wound repair. Targeted inhibition of the alternative pathway may represent a therapeutic modality for treating acute phases of IBD.

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Section: Discussionmentioning

confidence: 99%

Complement-Dependent Injury and Protection in a Murine Model of Acute Dextran Sulfate Sodium-Induced Colitis

Schepp-Berglind

Atkinson

Elvington

et al. 2012

The Journal of Immunology

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“…Additional studies found an association between low levels of MBL and severe forms of CD but not CD overall or UC (62). MBL deficiency was also associated with pediatric CD (63,64), although the association with UC in these populations was inconsistent. Understanding how the immune system maintains homeostasis within the intestinal tract, as well as the rest of the body, is a major point of investigation for immunologists.…”

Section: Discussionmentioning

confidence: 99%

Complement Activation by Giardia duodenalis Parasites through the Lectin Pathway Contributes to Mast Cell Responses and Parasite Control

Tako

Singer

2016

Infect Immun

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Infection with Giardia duodenalis is one of the most common causes of diarrheal disease in the world. While numerous studies have identified important contributions of adaptive immune responses to parasite control, much less work has examined innate immunity and its connections to the adaptive response during this infection. We explored the role of complement in immunity to Giardia using mice deficient in mannose-binding lectin (Mbl2) or complement factor 3a receptor (C3aR). Both strains exhibited delayed clearance of parasites and a reduced ability to recruit mast cells in the intestinal submucosa. C3aR-deficient mice had normal production of antiparasite IgA, but ex vivo T cell recall responses were impaired. These data suggest that complement is a key factor in the innate recognition of Giardia and that recruitment of mast cells and activation of T cell immunity through C3a are important for parasite control. Giardia duodenalis is one of the most common protozoan infections of humans as well as other mammals throughout the world and is a leading cause of diarrheal disease in these species (1-3). Symptomatic infections occur in ϳ20 to 80% of humans with positive stool samples and are characterized by nausea, vomiting, epigastric pains, and diarrhea (1, 2, 4, 5). These symptoms are associated with nutrient malabsorption and can lead to weight loss and malnutrition in children, exposing this vulnerable group to failure to thrive and developmental problems (6, 7). Disease resolves spontaneously in Ͼ85% of cases. In certain cases, in spite of a healthy and fully developed immune system, the acute phase of the disease develops into chronic disease. In these cases, symptoms of the disease will reappear for short and recurrent periods (3,4,8). The mechanisms explaining interactions between the host and the parasite leading to parasite clearance and disease pathogenesis are poorly understood.Studies of immune responses against Giardia have demonstrated important roles for both innate and adaptive immunity (7, 9). Antibody production following infection is robust, and IgA is very effective at eliminating parasites (9). Antibody-independent roles of T cells can also eliminate infections (10). Early studies indicated that Giardia trophozoites are susceptible to killing by factors in nonimmune human serum, milk, and intestinal fluid (11-13). Recently, killing by normal serum was demonstrated to involve the lectin pathway (14), consistent with the expression of N-acetylglucosamine (GlcNAc) on the surface of trophozoites (15,16). Studies of cells of the innate immune system indicate that macrophages, dendritic cells, mast cells, and intestinal epithelial cells are all involved. In vitro macrophages have been shown to be capable of ingesting Giardia, and we recently showed that macrophages accumulate in the lamina propria following infection (17, 18). Bone marrow-derived dendritic cells mature in response to Giardia extracts, but cytokine production in response to Toll-like receptor (TLR) agonists is modulated toward interle...

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“…11 An association between MBL-deficiency and antiyeast antibodies (ASCA) is observed in Crohn's disease (CD), and this deficiency is frequently associated with a severe phenotype of CD. 12,13 Furthermore, CD patients are more frequently colonized by C. albicans than control subjects. 14 Experimental studies show that C. albicans aggravates intestinal inflammation induced by dextran sulfate sodium (DSS) in mice, and conversely, DSS colitis promotes C. albicans colonization.…”

Section: Introductionmentioning

confidence: 99%

Role of mannose-binding lectin in intestinal homeostasis and fungal elimination

et al. 2016

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Mannose-binding lectin (MBL) is a soluble lectin of the innate immune system that is produced by the liver and secreted into the circulation where it activates the lectin complement pathway, enhances phagocytosis of microorganisms by leukocytes, and modulates inflammation. MBL can recognize patterns on the surface of different pathogens, including Candida albicans. Our aims were to investigate whether MBL is expressed in the gut epithelium and to examine its effect on the modulation of intestinal inflammation and C. albicans elimination. Using reverse transcriptase-PCR, MBL transcripts were highly expressed in different parts of the mouse gut. MBL expression was also detected by immunoblotting and immunolocalization in response to C. albicans colonization of the gut; the highest expression of MBL was detected in the stomach. Blocking MBL by administering mannans to mice increased C. albicans colonization. MBL-deficient mice had a higher level of colonization than wild-type mice. Dextran sodium sulfate-induced colitis promoted C. albicans dissemination to the kidneys and lungs of MBL-deficient mice. MBL-deficient mice exhibited elevated expression of interleukin (IL)-17, IL-23, dectin-1, and Toll-like receptor-4. This study shows that MBL expression is induced in the gut in response to C. albicans sensing and is required for intestinal homeostasis and host defense against C. albicans.

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Mannan-binding lectin deficiency in pediatric patients with inflammatory bowel disease

Abstract: These data suggest that MBL deficiency may be associated with CD but not with UC in pediatric patients. The possible role of MBL in IBD requires confirmation in larger series and further investigation of the mechanisms involved.

Cited by 26 publications

References 8 publications

Complement-Dependent Injury and Protection in a Murine Model of Acute Dextran Sulfate Sodium-Induced Colitis

Complement-Dependent Injury and Protection in a Murine Model of Acute Dextran Sulfate Sodium-Induced Colitis

Complement Activation by Giardia duodenalis Parasites through the Lectin Pathway Contributes to Mast Cell Responses and Parasite Control

Role of mannose-binding lectin in intestinal homeostasis and fungal elimination

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