L-MBP Is Expressed in Epithelial Cells of Mouse Small Intestine

Uemura, Kazuhide; Saka, Masako; Nakagawa, Toshimasa; Kawasaki, Norioki; Thiel, Steffen; Jensenius, Jens Christian; Kawasaki, Toshisuke

doi:10.4049/jimmunol.169.12.6945

Cited by 82 publications

(63 citation statements)

References 35 publications

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“…Also, these mice showed an impaired bacterial clearance from organs, indicating a clear need for further complement activation for the successful defense against infections. Interestingly, MBL-C is expressed in epithelial cells of the mouse small intestine, possibly indicating a role in mucosal immunity (46). However, MBL-A and MBL-C expression was also found in other tissues (51).…”

Section: Discussionmentioning

confidence: 99%

“…The concentration in serum of mouse MBL-C is about sixfold higher than that of MBL-A, and a mild increase in the levels of MBL-A was observed after injection of the acute-phase inducers (24,37). The liver is the main source of MBL biosynthesis, but expression was also shown in other tissues (46,51). Opsonization (22) and activation of the complement system via the lectin pathway (18,21) seem to be the main biological MBL functions.…”

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confidence: 99%

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Involvement of the Lectin Pathway of Complement Activation in Antimicrobial Immune Defense during Experimental Septic Peritonitis

et al. 2004

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A critical first line of defense against infection is constituted by the binding of natural antibodies to microbial surfaces, activating the complement system via the classical complement activation pathway. In this function, the classical activation pathway is supported and amplified by two antibody-independent complement activation routes, i.e., the lectin pathway and the alternative pathway. We studied the contribution of the different complement activation pathways in the host defense against experimental polymicrobial peritonitis induced by cecal ligation and puncture by using mice deficient in either C1q or factors B and C2. The C1q-deficient mice lack the classical complement activation pathway. While infection-induced mortality of wild-type mice was 27%, mortality of C1q-deficient mice was increased to 60%. Mice with a deficiency of both factors B and C2 lack complement activation via the classical, the alternative, and the lectin pathways and exhibit a mortality of 92%, indicating a significant contribution of the lectin and alternative pathways of complement activation to survival. For 14 days after infection, mannan-binding lectin (MBL)-dependent activation of C4 was compromised. Serum MBL-A and MBL-C levels were significantly reduced for 1 week, possibly due to consumption. mRNA expression profiles did not lend support for either of the two MBL genes to respond as typical acute-phase genes. Our results demonstrate a long-lasting depletion of MBL-A and MBL-C from serum during microbial infection and underline the importance of both the lectin and the alternative pathways for antimicrobial immune defense.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Involvement of the Lectin Pathway of Complement Activation in Antimicrobial Immune Defense during Experimental Septic Peritonitis

et al. 2004

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“…Mbl2 is abundantly expressed in epithelial cells of the small intestine, to which Giardia attaches and with which it interacts (24,29). MBL has been shown to bind to surface carbohydrates on pathogens, including Giardia, leading to complement activation (14).…”

Section: Resultsmentioning

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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“…Many innate immune factors are present in the gut, and some selectively target specific bacterial populations (14)(15)(16). The synthesis of surface polysaccharides is correlated directly with the ability of many bacteria to resist the bactericidal effects of a particular innate immune factor, complement (17)(18)(19).…”

Section: Survival Of Acapsular Mutant Under Conditions Simulating Thementioning

confidence: 99%

Role of glycan synthesis in colonization of the mammalian gut by the bacterial symbiont Bacteroides fragilis

Coyne

Chatzidaki‐Livanis

Paoletti

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

103

104

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Bacteroides species are the most abundant Gram-negative bacteria of the human colonic microbiota. These endogenous organisms are unique in that they synthesize an extensive number of phase-variable surface polysaccharides. Pathogenic bacteria phase vary expression of surface molecules for immune evasion, but the importance of the synthesis of multiple phase-variable polysaccharides to these commensal bacteria is unknown. We previously showed that a Bacteroides fragilis mutant unable to synthesize 4 of the 8 capsular polysaccharides and unable to glycosylate proteins properly is rapidly outcompeted by the wild-type strain for colonization of the gnotobiotic mouse intestine. In the present study, we constructed mutants defective only in capsule polysaccharide synthesis to define better the importance of these surface molecules to intestinal colonization. We discovered a key enzymatic activity required for synthesis of 7 of the 8 capsular polysaccharides. Deletion of its gene resulted in the first B. fragilis mutant able to synthesize only one phase-variable polysaccharide, and further mutation resulted in a stable acapsular mutant. We show that the acapsular mutant is rapidly outcompeted, but synthesis of a single polysaccharide is sufficient for the organism to colonize the gnotobiotic intestine competitively. These data demonstrate that initial colonization of the gnotobiotic mouse intestine by B. fragilis requires that the organism synthesize only a single polysaccharide and suggest that the synthesis of multiple phase-variable polysaccharides is important for the bacteria's long-term maintenance in the normally complex and competitive ecosystem. acapsular ͉ microbiota ͉ phase variation ͉ polysaccharide ͉ glycoprotein T he human intestinal tract is home to a vast and diverse alliance of microbes comprising one of the densest microbial ecosystems in the world and one that provides functions essential to human health. Many species of the order Bacteroidales are abundant members of the human intestinal microbiota and have served as models for studying mutualistic bacterial-host relationships in this ecosystem (1, 2). Despite their importance, relatively little is known about the biology of the predominant members of this ecosystem. Deciphering how these mutualistic microorganisms successfully and stably colonize the human intestine may help us understand how they are tolerated, how different members interact with one another, what additional benefits the microbiota provide us, and how microbiotaassociated diseases are triggered in the susceptible host.The intestinal Bacteroidales synthesize a vast repertoire of surface glycans. A single strain of B. fragilis synthesizes 8 distinct capsular polysaccharides (3), an extracellular polysaccharide (4), and numerous glycoproteins (5). The synthesis of extensive numbers of glycosylated molecules is a general property of the intestinal Bacteroidales (6-8). We estimate that the genome of B. fragilis 9343 encodes Ϸ80 glycosyltransferases and dedicates at least 215,000 bp of ...

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L-MBP Is Expressed in Epithelial Cells of Mouse Small Intestine

Cited by 82 publications

References 35 publications

Involvement of the Lectin Pathway of Complement Activation in Antimicrobial Immune Defense during Experimental Septic Peritonitis

Involvement of the Lectin Pathway of Complement Activation in Antimicrobial Immune Defense during Experimental Septic Peritonitis

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

Role of glycan synthesis in colonization of the mammalian gut by the bacterial symbiont Bacteroides fragilis

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