Mannose-Binding Lectin A-Deficient Mice Have Abrogated Antigen-Specific IgM Responses and Increased Susceptibility to a Nematode Infection

Carter, Tim; Sumiya, M.; Reilly, Kerri; Ahmed, Rubina; Sobieszczuk, Peter; Summerfield, John A.; Lawrence, Rachel A.

doi:10.4049/jimmunol.178.8.5116

Cited by 34 publications

(50 citation statements)

References 37 publications

(35 reference statements)

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“…17 Recent studies on MBL-deficient mice exposed to mf of Brugia malayi -another human filarial parasite-showed that the mf survived for significantly longer time periods in these when compared with wild-type mice. 33 The MBL is known to be an important component of innate immunity toward microbes by activating complement and augmenting opsonization and phagocytosis. 19,29 Whether MBL deficiency increases susceptibility to filarial infection by preventing these mechanisms, and the role played by MBL in innate immunity to these infections, should be important foci of further studies.…”

Section: Discussionmentioning

confidence: 99%

Association between Mannose-Binding Lectin Polymorphisms and Wuchereria bancrofti Infection in Two Communities in North-Eastern Tanzania

Meyrowitsch¹,

Simonsen²,

Garred³

et al. 2010

The American Journal of Tropical Medicine and Hygiene

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Abstract. The association between selected mannose-binding lectin (MBL) genotype polymorphisms and Wuchereria bancrofti infection status was assessed among individuals whose infection status had been monitored for three decades. Blood samples were collected in 2006 and examined for polymorphisms in the mbl-2 gene and for W. bancrofti -specific circulating filarial antigen (CFA) status. Logistic regression analysis showed a significant association between MBL genotype and CFA status, with low-expression MBL genotype individuals being almost three times more likely to be CFA positive than high-expression MBL genotype individuals (odds ratio [OR] = 2.90). When individuals' filarial infection (microfilaria) status in 1975 was included in the analyses, the gain of new infections between the two examination points was almost 10 times higher among individuals with low than among those with high MBL expression genotype (OR = 9.51). The susceptibility to W. bancrofti infection thus appears to be significantly affected by the MBL expression genotype of the host.

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Section: Discussionmentioning

confidence: 99%

Association between Mannose-Binding Lectin Polymorphisms and Wuchereria bancrofti Infection in Two Communities in North-Eastern Tanzania

Meyrowitsch¹,

Simonsen²,

Garred³

et al. 2010

The American Journal of Tropical Medicine and Hygiene

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“…Although roles for early Ag-specific IgM responses in the pathogenesis of allergic diseases remain to be delineated, in anthelminthic immunity, there are strong indications that early anthelminthic IgM responses are important [21,22]. Notably, eosinophil deficits in IL-5 knockout (KO) mice abrogated development of IgM-mediated, protective immunity to larval Strongyloides stercoralis [23,24].…”

Section: Discussionmentioning

confidence: 99%

Pivotal Advance: Eosinophils mediate early alum adjuvant-elicited B cell priming and IgM production

Wang

Weller

2008

Journal of Leukocyte Biology

102

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Alum, aluminum-hydroxide-containing compounds, long used as adjuvants in human vaccinations, functions by ill-defined, immunostimulatory mechanisms. Antigen-free alum has been shown to act via a previously unidentified, splenic Gr1 + , IL-4-expressing myeloid cell population to stimulate early B cell priming. We demonstrate that the alum-elicited and -activated splenic myeloid cells are IL-4-expressing eosinophils that function to prime B cell responses. Eosinophils are the principal Gr1 + , IL-4 + cells in the spleens 6 days following i.p. alum administration. Alum-elicited splenic B cell priming, as evidenced by MHC II cross-linkingmediated calcium mobilization developed in wild-type BALB/c mice, was absent in ΔdblGATA BALB/c eosinophil-deficient mice and could be reconstituted by adoptive eosinophil infusions into the eosinophil-deficient mice. Moreover, early antigen-specific IgM antibody responses in alum-antigen-immunized mice were impaired in eosinophil-deficient mice and were restored with adoptive transfers of eosinophils. Thus, eosinophils, leukocytes of the innate immune system that contain preformed cytokines, including IL-4, have novel, immunomodulatory roles in the initial priming of B cells elicited by the adjuvant alum and in the optimal early B cell generation of antigen-specific IgM.

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“…MBL has been shown to bind to surface carbohydrates on pathogens, including Giardia, leading to complement activation (14). In many infections, this recognition has a significant influence on disease outcome, e.g., in cryptosporidiosis, leishmaniasis, malaria, and HIV infection (30)(31)(32)(33). Interestingly, several studies have established a link between human genotypes associated with low serum levels of MBL and susceptibility to severe infectious diseases such as malaria, HIV, and cryptococcosis (34)(35)(36).…”

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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Mannose-Binding Lectin A-Deficient Mice Have Abrogated Antigen-Specific IgM Responses and Increased Susceptibility to a Nematode Infection

Cited by 34 publications

References 37 publications

Association between Mannose-Binding Lectin Polymorphisms and Wuchereria bancrofti Infection in Two Communities in North-Eastern Tanzania

Association between Mannose-Binding Lectin Polymorphisms and Wuchereria bancrofti Infection in Two Communities in North-Eastern Tanzania

Pivotal Advance: Eosinophils mediate early alum adjuvant-elicited B cell priming and IgM production

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

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