scholarly journals Natural Antibody Affects Survival of the SpirocheteBorrelia burgdorferi within Feeding Ticks

2001 ◽  
Vol 69 (10) ◽  
pp. 6456-6462 ◽  
Author(s):  
Alexia A. Belperron ◽  
Linda K. Bockenstedt
Keyword(s):  
Salivary Gland ◽  
B Cell ◽  
Pathogen Transmission ◽  
Natural Antibodies ◽  
Immunoglobulin M ◽  
Mouse Serum ◽  
Mammalian Host ◽  
Tick Feeding ◽  
Blood Sucking ◽  
Deficient Mice

ABSTRACT Natural antibodies are those immunoglobulin molecules found in mammalian serum that arise in the absence of exposure to environmental pathogens and may comprise an early host defense against invading pathogens. The spirochete Borrelia burgdorferi first encounters natural antibodies when its arthropod vector, Ixodes scapularis, begins feeding on a mammalian host. Natural antibodies may therefore have an impact on pathogens within blood-sucking vectors, prior to pathogen transmission to the mammal. In this study, we investigated whether natural antibodies influenced the number and/or phenotype of B. burgdorferi organisms within feeding I. scapularis nymphs. Using a competitive PCR, we found that ticks ingesting a blood meal from B-cell-deficient mice, which lack all immunoglobulins, contained fivefold more spirochete DNA than ticks feeding on control mice. Spirochete DNA levels could be reduced to that of controls with passive transfer of normal mouse serum or polyclonal immunoglobulin M (IgM), but not IgG, into B-cell-deficient mice prior to placement of infected ticks. At 48 h of tick feeding, 90% of spirochetes within salivary glands of ticks removed from B-cell-deficient mice were found by confocal immunofluorescence microscopy to express outer surface protein A (OspA), compared to only 5% of salivary gland spirochetes from ticks detached from control mice. Taken together, these results show that ingestion of natural antibodies limits the spirochete burden within feeding ticks. Because OspA is normally downregulated when spirochetes moved from the tick midgut to the salivary gland, our findings suggest that OspA-expressing midgut spirochetes may be particularly susceptible to the borrelicidal effects of these molecules.

scholarly journals A tumor-suppressor function for Fas (CD95) revealed in T cell-deficient mice.

1996 ◽  
Vol 184 (3) ◽  
pp. 1149-1154 ◽  
Author(s):  
S L Peng ◽  
M E Robert ◽  
A C Hayday ◽  
J Craft
Keyword(s):  
T Cells ◽  
Tumor Suppressor ◽  
B Cell ◽  
Malignant Tumors ◽  
B Cell Lymphoma ◽  
Immunoglobulin M ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Alpha Beta ◽  
Deficient Mice

Fas (CD95) and its ligand are central regulatory molecules in hematopoietic cells. Previous studies have suggested a role for Fas in the regulation of tumor progression, but Fas has not yet been conclusively identified as a tumor suppressor. Fas-deficient individuals lack malignant tumors, perhaps because of regulation by T cells. To investigate such a possibility, mice deficient in both T cells and Fas were generated, and they were found to develop severe B cell dysregulation characterized by malignant, lethal B cell lymphoma. Lymphoma arose from a monoclonal B220+CD19-CD5-CD23- B cell secreting immunoglobulin M, kappa rheumatoid factor. In contrast, animals containing alpha beta T cells, gamma delta T cells, and/or functional Fas suppressed the development of lymphoma. These data indicate that Fas functions as a tumor suppressor, and identifies roles for both alpha beta T cells and gamma delta T cells in Fas-independent tumor regulation.

scholarly journals Surface Sialic Acids Taken from the Host Allow Trypanosome Survival in Tsetse Fly Vectors

2004 ◽  
Vol 199 (10) ◽  
pp. 1445-1450 ◽  
Author(s):  
Kisaburo Nagamune ◽  
Alvaro Acosta-Serrano ◽  
Haruki Uemura ◽  
Reto Brun ◽  
Christina Kunz-Renggli ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Trypanosoma Brucei ◽  
Sialic Acids ◽  
Sleeping Sickness ◽  
Tsetse Fly ◽  
Mammalian Host ◽  
Tsetse Flies ◽  
African Trypanosome ◽  
Blood Sucking

The African trypanosome Trypanosoma brucei, which causes sleeping sickness in humans and Nagana disease in livestock, is spread via blood-sucking Tsetse flies. In the fly's intestine, the trypanosomes survive digestive and trypanocidal environments, proliferate, and translocate into the salivary gland, where they become infectious to the next mammalian host. Here, we show that for successful survival in Tsetse flies, the trypanosomes use trans-sialidase to transfer sialic acids that they cannot synthesize from host's glycoconjugates to the glycosylphosphatidylinositols (GPIs), which are abundantly expressed on their surface. Trypanosomes lacking sialic acids due to a defective generation of GPI-anchored trans-sialidase could not survive in the intestine, but regained the ability to survive when sialylated by means of soluble trans-sialidase. Thus, surface sialic acids appear to protect the parasites from the digestive and trypanocidal environments in the midgut of Tsetse flies.

Alterations of serum protein N-glycosylation in two mouse models of chronic liver disease are hepatocyte and not B cell driven

2011 ◽  
Vol 300 (5) ◽  
pp. G833-G842 ◽  
Author(s):  
Bram Blomme ◽  
Christophe Van Steenkiste ◽  
Paola Grassi ◽  
Stuart M. Haslam ◽  
Anne Dell ◽  
...  
Keyword(s):  
Liver Disease ◽  
B Cell ◽  
Chronic Liver Disease ◽  
Mouse Models ◽  
Chronic Liver ◽  
Mouse Serum ◽  
Total Serum ◽  
Glycan Analysis ◽  
The Impact ◽  
Deficient Mice

N-glycosylation of immunoglobulin G (IgG) has an important impact on the modification of the total serum N-glycome in chronic liver patients. Our aim was to determine the role and magnitude of the alterations in which hepatocytes and B cells are involved in two mouse models of chronic liver disease. Common bile duct ligation (CBDL) and subcutaneous injections with CCl4 were induced in B cell-deficient and wild-type (WT) mice. IgG depletion was performed with beads covered with protein A/G and the depletions were evaluated by SDS-PAGE and Western blot analysis. N-glycan analysis was performed by improved DSA-FACE technology. Structural analysis of the mouse serum N-glycans was performed by exoglycosidase digests and MALDI-TOF mass spectrometry of permethylated glycans. The alterations seen in B cell-deficient mice closely resembled the alterations in WT mice, in both the CBDL and the CCl4 models. N-glycan analysis of the IgG fraction in both mouse models revealed different changes compared with humans. Overall, the impact of IgG glycosylation on total serum glycosylation was marginal. Interestingly, the amount of fibrosis present in CBDL B cell-deficient mice was significantly increased compared with CBDL WT mice, whereas the opposite was true for the CCl4 model as determined by Sirius red staining. However, this had no major effect on the alteration of N-glycosylation of serum proteins. Alterations of total serum N-glycome in mouse models of chronic liver disease are hepatocyte-driven. Undergalactosylation of IgG is not present in mouse models of chronic liver disease.

scholarly journals A Critical Role of Natural Immunoglobulin M in Immediate Defense Against Systemic Bacterial Infection

1998 ◽  
Vol 188 (12) ◽  
pp. 2381-2386 ◽  
Author(s):  
Marianne Boes ◽  
Andrey P. Prodeus ◽  
Tara Schmidt ◽  
Michael C. Carroll ◽  
Jianzhu Chen
Keyword(s):  
Bacterial Infection ◽  
Bacterial Load ◽  
Critical Role ◽  
Cecal Ligation ◽  
Immunoglobulin M ◽  
Mouse Serum ◽  
Microbial Infection ◽  
Acute Peritonitis ◽  
Deficient Mice

To evaluate the role of natural immunoglobulin (Ig)M in the immediate response against microbial infection, we tested mutant mice that are deficient in secreted (s)IgM in an acute peritonitis model induced by cecal ligation and puncture (CLP). 20% of wild-type mice died within 32 h of CLP, whereas 70% of sIgM-deficient mice died within the same time period. The increased susceptibility was associated with a reduced level of tumor necrosis factor (TNF)-α, a decreased neutrophil recruitment and an increased bacterial load in the peritoneum, and elevated levels of endotoxin and proinflammatory cytokines in the circulation. Resistance to CLP by sIgM-deficient mice was restored by reconstitution with polyclonal IgM from normal mouse serum. Reconstitution with a monoclonal IgM specific to phosphatidylcholine, a conserved cell membrane component, has a modest effect but a monoclonal IgM specific to phosphocholine is not protective. These findings demonstrate a critical role of natural IgM in the immediate defense against severe bacterial infection.

scholarly journals Probing the Rhipicephalusbursa Sialomes in Potential Anti-Tick Vaccine Candidates: A Reverse Vaccinology Approach

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 363
Author(s):  
Joana Couto ◽  
Gonçalo Seixas ◽  
Christian Stutzer ◽  
Nicholas A. Olivier ◽  
Christine Maritz-Olivier ◽  
...  
Keyword(s):  
Immune Response ◽  
In Silico ◽  
Reverse Genetics ◽  
Pathogen Transmission ◽  
Reverse Vaccinology ◽  
Mammalian Host ◽  
T Cell Epitopes ◽  
Tick Feeding ◽  
Vaccine Candidates

In the wake of the ‘omics’ explosion of data, reverse vaccinology approaches are being applied more readily as an alternative for the discovery of candidates for next generation diagnostics and vaccines. Promising protective antigens for the control of ticks and tick-borne diseases can be discovered by mining available omics data for immunogenic epitopes. The present study aims to explore the previously obtained Rhipicephalus bursa sialotranscriptome during both feeding and Babesia infection, to select antigenic targets that are either membrane-associated or a secreted protein, as well as unique to the ectoparasite and not present in the mammalian host. Further, they should be capable of stimulating T and B cells for a potential robust immune response, and be non-allergenic or toxic to the host. From the R. bursa transcriptome, 5706 and 3025 proteins were identified as belonging to the surfaceome and secretome, respectively. Following a reverse genetics immunoinformatics pipeline, nine preferred candidates, consisting of one transmembrane-related and eight secreted proteins, were identified. These candidates showed a higher predicted antigenicity than the Bm86 antigen, with no homology to mammalian hosts and exposed regions. Only four were functionally annotated and selected for further in silico analysis, which examined their protein structure, surface accessibility, flexibility, hydrophobicity, and putative linear B and T-cell epitopes. Regions with overlapping coincident epitopes groups (CEGs) were evaluated to select peptides that were further analyzed for their physicochemical characteristics, potential allergenicity, toxicity, solubility, and potential propensity for crystallization. Following these procedures, a set of three peptides from the three R. bursa proteins were selected. In silico results indicate that the designed epitopes could stimulate a protective and long-lasting immune response against those tick proteins, reflecting its potential as anti-tick vaccines. The immunogenicity of these peptides was evaluated in a pilot immunization study followed by tick feeding to evaluate its impact on tick behavior and pathogen transmission. Combining in silico methods with in vivo immunogenicity evaluation enabled the screening of vaccine candidates prior to expensive infestation studies on the definitive ovine host animals.

scholarly journals Tick extracellular vesicles enable arthropod feeding and promote distinct outcomes of bacterial infection

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Adela S. Oliva Chávez ◽  
Xiaowei Wang ◽  
Liron Marnin ◽  
Nathan K. Archer ◽  
Holly L. Hammond ◽  
...  
Keyword(s):  
Bacterial Infection ◽  
Extracellular Vesicles ◽  
Ixodes Scapularis ◽  
Pathogen Transmission ◽  
Snare Proteins ◽  
Mammalian Host ◽  
Tick Feeding ◽  
Vector Borne Diseases ◽  
Skin Immunity ◽  
Vector Borne

AbstractExtracellular vesicles are thought to facilitate pathogen transmission from arthropods to humans and other animals. Here, we reveal that pathogen spreading from arthropods to the mammalian host is multifaceted. Extracellular vesicles from Ixodes scapularis enable tick feeding and promote infection of the mildly virulent rickettsial agent Anaplasma phagocytophilum through the SNARE proteins Vamp33 and Synaptobrevin 2 and dendritic epidermal T cells. However, extracellular vesicles from the tick Dermacentor andersoni mitigate microbial spreading caused by the lethal pathogen Francisella tularensis. Collectively, we establish that tick extracellular vesicles foster distinct outcomes of bacterial infection and assist in vector feeding by acting on skin immunity. Thus, the biology of arthropods should be taken into consideration when developing strategies to control vector-borne diseases.

Investigation of Tickborne Pathogens within Naturally Infected Brown Dog Tick (Ixodidae: Rhipicephalus Sanguineus) in Egypt by Light and Electron Microscopy

2020 ◽  
Keyword(s):  
Electron Microscopy ◽  
Salivary Gland ◽  
Light And Electron Microscopy ◽  
Rhipicephalus Sanguineus ◽  
Mammalian Host ◽  
Babesia Canis ◽  
Brown Dog Tick ◽  
Transmission Electron ◽  
Dog Tick ◽  
Theileria Spp

Tick borne pathogens present a significant health challenge to animals and human because a single tick may transmit multiple pathogens to a mammalian host during feeding. The present study detected tick-borne pathogens from pet dogs. A total of 666 ticks were collected from 144 pet and sheltered dogs in Egypt from April to September 2018. For hemolymph, midgut and salivary gland smears 546 ticks were used as well as 360 egg smears from 120 female tick were examined by light microscope. The infected ticks were prepared for transmission electron microscopy (TEM). Ticks were identified; Rhipicephalus sanguineus. Light microscopy showed infection rates of 44.69%, 68.50% & 15.75%, in hemolymph, midgut and salivary gland, respectively. H. canis recorded the highest rates in hemolymph and midgut (35.89% & 49.82%, respectively), but Theileria spp. was the lowest (0.73% & 2.93%, respectively). In salivary gland smears, Babesia canis. was detected in 13.55% and Theileria spp. in 1.83%. Mixed infection in same tick was recorded in 4.76% &0.37% in midgut and salivary gland smears, respectively. Babesia canis stages were recovered from 15% of egg smears. R. sanguineus was natural infected by Babesia, Theileria, Hepatozoon and Anaplasma phagocytophilum as well as mixed infections of protozoa accompanied by a complicated sign of diseases and failure in accurate diagnosis.

scholarly journals Altered Erythrocytes and a Leaky Block in B-Cell Development in CD24/HSA-Deficient Mice

Blood ◽  
1997 ◽  
Vol 89 (3) ◽  
pp. 1058-1067 ◽  
Author(s):  
P.J. Nielsen ◽  
B. Lorenz ◽  
A.M. Müller ◽  
R.H. Wenger ◽  
F. Brombacher ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
B Cell ◽  
Embryonic Stem ◽  
Cell Development ◽  
B Cell Development ◽  
Surface Glycoprotein ◽  
Malarial Parasite ◽  
Heat Stable Antigen ◽  
Deficient Mice

Abstract The heat stable antigen (HSA, or murine CD24) is a glycosyl phosphatidylinositol-linked surface glycoprotein expressed on immature cells of most, if not all, major hematopoietic lineages, as well as in developing neural and epithelial cells. It has been widely used to stage the maturation of B and T lymphocytes because it is strongly induced and then repressed again during their maturation. Terminally differentiated lymphocytes, as well as most myeloid lineages, are negative for HSA. Erythrocytes are an exception in that they maintain high levels of HSA expression. HSA on naive B cells has been shown to mediate cell-cell adhesion, while HSA on antigen-presenting cells has been shown to mediate a costimulatory signal important for activating T lymphocytes during an immune response. Here, we characterize mice that lack a functional HSA gene, constructed by homologous recombination in embryonic stem cells. While T-cell and myeloid development appears normal, these mice show a leaky block in B-cell development with a reduction in late pre-B and immature B-cell populations in the bone marrow. Nevertheless, peripheral B-cell numbers are normal and no impairment of immune function could be detected in these mice in a variety of immunization and infection models. We also observed that erythrocytes are altered in HSA-deficient mice. They show a higher tendency to aggregate and are more susceptible to hypotonic lysis in vitro. In vivo, the mean half-life of HSA-deficient erythrocytes was reduced. When infected with the malarial parasite Plasmodium chabaudi chabaudi, the levels of parasite-bearing erythrocytes in HSA-deficient mice were also significantly elevated, but the mice were able to clear the infection with kinetics similar to wild-type mice and were immune to a second challenge. Thus, apart from alterations in erythrocytes and a mild block in B-cell development, the regulated expression of HSA appears to be dispensable for the maturation and functioning of those cell lineages that normally express it.

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