scholarly journals Cotton Rat Placenta Anatomy and Fc Receptor Expression and Their Roles in Maternal Antibody Transfer

2020 ◽  
Vol 70 (6) ◽  
pp. 510-519
Author(s):  
Margaret E Martinez ◽  
Stefan Niewiesk ◽  
Krista M D La Perle
Keyword(s):  
Fc Receptors ◽  
Fc Receptor ◽  
Yolk Sac ◽  
Maternal Antibody ◽  
Maternal Antibodies ◽  
Structural Basis ◽  
Cotton Rat ◽  
Chorionic Plate ◽  
Rsv Infection ◽  
Cotton Rats

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and viral pneumonia in infants and young children worldwide. Currently no vaccine is available to prevent RSV infection, but virus-neutralizing monoclonal antibodies can be given prophylactically, emphasizing the protective potential of antibodies. One concept of RSV vaccinology is mothers' immunization to induce high antibody titers, leading to passive transfer of high levels of maternal antibody to the fetus through the placenta and to the neonate through colostrum. Cotton rats are an excellent small animal model for RSV infection and have been used to test maternal immunization. To mechanistically understand antibody transfer in the cotton rat model, we characterized the cotton rat placenta and Fc receptor localization. Placentas from cotton rats at midgestation (approximately day 14) and at late gestation (approximately day 25) and neonatal (younger than 1 wk) gastrointestinal tracts were collected for light microscopy, immunohistochemistry, and transmission electron microscopy. The cotton rat placenta is hemotrichorial and has 5 distinct layers: decidua, junctional zone, labyrinth, chorionic plate, and yolk sac. Consistent with the transfer of maternal antibodies, the majority of the Fc receptors are present in the yolk sac endoderm and fetal capillary endothelium of the chorionic plate, involving 10% of the cells within the labyrinth. In addition, Fc receptors are present on duodenal and jejunal enterocytes in cotton rats, similar to humans, mice, and rats. These findings provide the structural basis for the pre- and postnatal transfer of maternal antibodies described in cotton rats.

scholarly journals Comparisons of Antibody Populations in Different Pre-Fusion F VLP-Immunized Cotton Rat Dams and Their Offspring

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 133 ◽  
Author(s):  
Lori M. Cullen ◽  
Marina S. Boukhvalova ◽  
Jorge C. G. Blanco ◽  
Trudy G. Morrison
Keyword(s):  
Fusion Proteins ◽  
Significant Risk ◽  
Maternal Antibodies ◽  
Protein Targets ◽  
Cotton Rat ◽  
F Protein ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Blocking Antibodies ◽  
Better Than

Respiratory syncytial virus (RSV) infection poses a significant risk for infants. Since the direct vaccination of infants is problematic, maternal vaccination may provide a safer, more effective approach to their protection. In the cotton rat (CR) model, we have compared the immunization of pregnant CR dams with virus-like particles assembled with the prototype mutation stabilized pre-fusion F protein, DS-Cav1, as well two alternative mutation stabilized pre-fusion proteins (UC-2 F, UC-3 F) and showed that the alternative pre-fusion F VLPs protected the offspring of immunized dams significantly better than DS-Cav1 F VLPs (Blanco, et al. J. Virol. 93: e00914). Here, we have addressed the reasons for this increased protection by characterizing the specificities of antibodies in the sera of both immunized dams and their offspring. The approach was to measure the levels of total anti-pre-F IgG serum antibodies that would block the binding of representative pre-fusion specific monoclonal antibodies to soluble pre-fusion F protein targets. Strikingly, we found that the sera in most offspring of DS-Cav1 F VLP-immunized dams had no mAb D25-blocking antibodies, although their dams had robust levels. In contrast, all offspring of UC-3 F VLP-immunized dams had robust levels of these D25-blocking antibodies. Both sets of pup sera had significant levels of mAb AM14-blocking antibodies, indicating that all pups received maternal antibodies. A lack of mAb D25-blocking antibodies in the offspring of DS-Cav1 F VLP-immunized dams may account for the lower protection of their pups from challenge compared to the offspring of UC-3 F VLP-immunized dams.

scholarly journals CX3CR1 is a Receptor for Human Respiratory Syncytial Virus in Cotton Rats

2021 ◽  
Author(s):  
Gia Green ◽  
Sara M. Johnson ◽  
Heather Costello ◽  
Kelsey Brakel ◽  
Olivia Harder ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
G Protein ◽  
Airway Epithelial ◽  
Cotton Rat ◽  
Receptor Molecule ◽  
Human Airway ◽  
Rsv Infection ◽  
Cotton Rats ◽  
Syncytial Virus

Respiratory syncytial virus (RSV) has been reported to use CX3CR1 in vitro as a receptor on cultured primary human airway epithelial cultures. To evaluate CX3CR1 as the receptor for RSV in vivo , we used the cotton rat animal model because of its high permissiveness for RSV infection. Sequencing the cotton rat CX3CR1 gene revealed 91% amino acid similarity to human CX3CR1. Previous work found that RSV binds to CX3CR1 via its attachment glycoprotein (G protein) to infect primary human airway cultures. To determine whether CX3CR1-G protein interaction is necessary for RSV infection, recombinant RSVs containing mutations in the CX3CR1 binding site of the G protein were tested in cotton rats. In contrast to wildtype virus, viral mutants did not grow in the lungs of cotton rats. When RSV was incubated with an antibody blocking the CX3CR1 binding site of G protein and subsequently inoculated intranasally into cotton rats, no virus was found in the lungs four days post-infection. In contrast, growth of RSV was not affected after pre-incubation with heparan sulfate (the receptor for RSV on immortalized cell lines). A reduction in CX3CR1 expression in the cotton rat lung through the use of peptide-conjugated morpholino oligomers led to a 10-fold reduction in RSV titers at day four post-infection. In summary, these results indicate that CX3CR1 functions as a receptor for RSV in cotton rats, and in combination with data from human airway epithelial cell cultures, strongly suggest that CX3CR1 is a primary receptor for naturally acquired RSV infection. Importance The knowledge about a virus receptor is useful to better understand the uptake of a virus into a cell and potentially develop antivirals either directed against the receptor molecule on the cell or the receptor-binding protein of the virus. Amongst a number of potential receptor proteins, human CX3CR1 has been demonstrated to act as receptor for respiratory syncytial virus (RSV) on human epithelial cells in tissue culture. Here we report that the cotton rat CX3CR1 which is similar to the human molecule acts as receptor in vivo. This study strengthens the argument that CX3CR1 is a receptor molecule for RSV.

scholarly journals The Potential Role of Nonhuman Primate Models to Better Comprehend Early Life Immunity and Maternal Antibody Transfer

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 306
Author(s):  
Julie Sartoretti ◽  
Christiane S. Eberhardt
Keyword(s):  
Nonhuman Primate ◽  
Early Life ◽  
Cost Effective ◽  
Maternal Antibody ◽  
Maternal Antibodies ◽  
Immunological Methods ◽  
Human Pathogens ◽  
Childhood Immunization ◽  
Primate Model ◽  
The Impact

Early life immunity is a complex field of research and there are still gaps in knowledge regarding the detailed mechanism of maternal antibody transfer, the impact of maternal antibodies on infant vaccine responses and the ontogeny of human early life immunity. A comprehensive understanding is necessary to identify requirements for early life vaccines and to improve early childhood immunization. New immunological methods have facilitated performing research in the youngest, however, some questions can only be addressed in animal models. To date, mostly murine models are used to study neonatal and infant immunity since they are well-described, easy to use and cost effective. Given their limitations especially in the transfer biology of maternal antibodies and the lack of infectivity of numerous human pathogens, this opinion piece discusses the potential and prerequisites of the nonhuman primate model in studying early life immunity and maternal antibody transfer.

Evidence for Fc receptors on rabbit yolk sac endoderm

Nature ◽  
1977 ◽  
Vol 268 (5619) ◽  
pp. 443-445 ◽  
Author(s):  
A. E. WILD ◽  
PAT DAWSON
Keyword(s):  
Fc Receptors ◽  
Yolk Sac

scholarly journals Structural basis for pH-insensitive inhibition of immunoglobulin G recycling by an anti-neonatal Fc receptor antibody

2017 ◽  
Vol 292 (42) ◽  
pp. 17449-17460 ◽  
Author(s):  
Jon A. Kenniston ◽  
Brandy M. Taylor ◽  
Gregory P. Conley ◽  
Janja Cosic ◽  
Kris J. Kopacz ◽  
...  
Keyword(s):  
Immunoglobulin G ◽  
Fc Receptor ◽  
Structural Basis ◽  
Neonatal Fc Receptor ◽  
Receptor Antibody

The lymphocyte surface. II. Separation of Fc receptor, C'3 receptor and surface immunoglobulin-bearing lymphocytes

1974 ◽  
Vol 187 (1086) ◽  
pp. 65-81 ◽  
Keyword(s):  
Lymph Nodes ◽  
Thoracic Duct ◽  
Large Population ◽  
Fc Receptors ◽  
Fc Receptor ◽  
Substantial Proportion ◽  
Separation Procedure ◽  
Total Recovery ◽  
Surface Immunoglobulin ◽  
Spleen And Lymph Nodes

A one-step separation procedure is described for both depleting and obtaining in pure form Fc receptor (FcRL), C'3 receptor (CRL) and surface immunoglobulin bearing (IgL) lymphocytes from rat lymphoid populations. The method is a modification of the Bӧyum (1968) technique for separating lymphocytes from whole blood by sedimentation on Ficoll/Isopaque, and is based on the fact that when a lymphocyte forms a rosette with sensitized erythrocytes it will sediment with the red cells rather than float with the non-rosetting lymphocytes. The technique is > 99.5% efficient at depleting thoracic duct lymphocytes (TDL) of FcRL, CRL and IgL and these subpopulations can be recovered 93-98% pure. The total recovery of lymphocytes applied is usually > 90% and the separated lymphocytes are > 95% viable. This technique allowed the cellular distribution of Fc receptors, C'3 receptors and surface Ig to be determined. It was found that ( a ) Almost all CRL carry surface Ig, although a very small sub-population of CRL (0.2-0.8%) which lacks surface Ig could regularly be detected. ( b ) A substantial proportion of IgL (12-25%) lacks C'3 receptors. ( c ) IgL and CRL which lack Fc receptors are more frequent in spleen and lymph nodes than in TDL. The proportion of this subpopulation increases in TDL after prolonged thoracic duct drainage. ( d ) Some FcRL exist which lack both C'3 receptors and surface Ig. These cells are more evident in TDL after prolonged thoracic duct drainage and in lymph nodes (20-30% of FcRL) than in early TDL or spleen (5-10% of FcRL). ( e ) The thymus contains very few FcRL, CRL or IgL. ( f ) A large population of lymphocytes exists in B rats (32-42% of TDL) which is killed by an anti-B serum but which lacks surface Ig. These cells are much less frequent in normal TDL ( < 5%) and probably also lack Fc and C'3 receptors. ( g ) Large lymphocytes probably shed their Fc and C'3 receptors, but retain their surface Ig, during S-phase. ( h ) Studies on a secondary anti-DNP response showed that a substantial proportion of direct and indirect plaque forming cells (PFC) in the spleen express Fc receptors, whereas only indirect PFC carry C'3 receptors. Virtually all PFC ( > 98%) possess surface Ig.

scholarly journals Evolution of protection after maternal immunization for respiratory syncytial virus in cotton rats

2021 ◽  
Author(s):  
Jorge C.G. Blanco ◽  
Lori McGinnes-Cullen ◽  
Arash Kamali ◽  
Fatoumata Sylla ◽  
Marina Boukhavalova ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Neutralizing Antibody ◽  
Wild Type ◽  
Cotton Rat ◽  
Before And After ◽  
Boost Immunization ◽  
Cotton Rats ◽  
Antibody Titers ◽  
Syncytial Virus ◽  
Efficient Transfer

Maternal anti-respiratory syncytial virus (RSV) antibodies acquired by the fetus through the placenta protect neonates from RSV disease through the first weeks of life.  In the cotton rat model of RSV infections, we previously reported that immunization of dams during pregnancy with virus-like particles assembled with mutation stabilized pre-fusion F protein as well as the wild type G protein resulted in robust protection of their offspring from RSV challenge (Blanco, et al Journal of Virology 93: e00914-19, https://doi.org/10.1128/JVI.00914-19).  Here we describe the durability of those protective responses in dams, the durability of protection in offspring, and the transfer of that protection to offspring of two consecutive pregnancies without a second boost immunization.  We report that four weeks after birth, offspring of the first pregnancy were significantly protected from RSV replication in both lungs and nasal tissues after RSV challenge, but protection was reduced in pups at 6 weeks after birth.   However, the overall protection of offspring of the second pregnancy was considerably reduced, even at four weeks of age.  This drop in protection occurred even though the levels of total anti-pre-F IgG and neutralizing antibody titers in dams remained at similar, high levels before and after the second pregnancy.  The results are consistent with an evolution of antibody properties in dams to populations less efficiently transferred to offspring or the less efficient transfer of antibodies in elderly dams.

scholarly journals Effects of soluble immune complexes on Fc receptor- and C3b receptor-mediated phagocytosis by macrophages.

1980 ◽  
Vol 152 (4) ◽  
pp. 905-919 ◽  
Author(s):  
F M Griffin
Keyword(s):  
Immune Complexes ◽  
Fc Receptors ◽  
Fc Receptor ◽  
Complement Receptor ◽  
Complement Receptors ◽  
Phagocytic Function ◽  
Receptor Function ◽  
Coated Particles ◽  
C3b Receptor ◽  
Soluble Immune Complexes

The effects of ingestion of soluble immune complexes upon macrophage phagocytic function was studied. Ingestion of immune complexes severely impaired the macrophage's ability to ingest IgG-coated particles but did not alter its ability to interact with particles by means other than its Fc receptors. Treatment of macrophages that had ingested immune complexes with supernates containing the previously described lymphokine that augments macrophage complement receptor function failed to enhance the cells' interaction with either IgG-coated erythrocytes or zymosan particles but markedly enhanced their ability to phagocytize via their complement receptors. The possible significance of these findings in immunologically mediated inflammation is discussed.

scholarly journals Isolation and characterization of the Fc receptor from the fetal yolk sac of the rat.

1990 ◽  
Vol 111 (5) ◽  
pp. 1867-1876 ◽  
Author(s):  
D M Roberts ◽  
M Guenthert ◽  
R Rodewald
Keyword(s):  
Affinity Purification ◽  
Basolateral Membrane ◽  
Apical Cell ◽  
Protein Band ◽  
Fc Receptor ◽  
Yolk Sac ◽  
Neonatal Rat ◽  
Unexpected Finding ◽  
Isolation And Characterization ◽  
Maternal Igg

The yolk sac of the fetal rat and the proximal small intestine of the neonatal rat selectively transport maternal IgG. IgG-Fc receptors are thought to mediate transport across the epithelium of both tissues. We used a mouse mAb (MC-39) against the 45-54-kD component of the Fc receptor of the neonatal intestine to find an antigenically related protein that might function as an Fc receptor in fetal yolk sac. In immunoblots of yolk sac, MC-39 recognized a protein band with apparent molecular mass of 54-58 kD. MC-39 bound to the endoderm of yolk sac in immunofluorescence studies. In immunogold-labeling experiments MC-39 was associated mainly with small vesicles in the apical cytoplasm and in the region near the basolateral membrane of endodermal cells. The MC-39 cross-reactive protein and beta 2-microglobulin, a component of the intestinal Fc receptor, were copurified from detergent-solubilized yolk sac by an affinity purification that selected for proteins which, like the intestinal receptor, bound to IgG at pH 6.0 and eluted at pH 8.0. In summary, the data suggest that we have isolated the Fc receptor of the yolk sac and that this receptor is structurally and functionally related to the Fc receptor of the neonatal intestine. An unexpected finding is that, unlike the intestinal receptor which binds maternal IgG on the apical cell surface, the yolk sac receptor appears to bind IgG only within apical compartments which we suggest represent the endosomal complex.

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