Dataset Information

Development of atopy by severe paramyxoviral infection in a mouse model.

ABSTRACT:

Background

Atopic diseases have been increasing in prevalence, yet the initial inciting events that lead to atopy are not understood. Paramyxoviral infections have been suggested to play a role; however, much of these data are correlative.

Objective

To determine whether exposure to a nonviral antigen during a paramyxoviral infection is sufficient to drive IgE production against the bystander antigen and whether clinical disease against this antigen would result.

Methods

Wild-type C57BL6 mice or mice deficient in Fc?RI? (Fc?RI?(-/-)) or IgE (IgE(-/-)) were inoculated with Sendai virus (SeV) or UV-inactivated SeV (UV-SeV) and subsequently exposed to ovalbumin (OVA) intranasally. Mice were further challenged 3 times with intranasal OVA on days 20 to 22 after inoculation with SeV, and airway hyperreactivity and mucous cell metaplasia were determined.

Results

Exposure to OVA during SeV infection led to significant OVA specific IgE production (median, 548 vs 0 ng/mL; P = .03; SeV vs UV-SeV). This induction of OVA specific IgE production depended on Fc?RI because Fc?RI?(-/-) mice produced significantly less IgE (112 ng/mL; P = .03; vs wild-type mice). Furthermore, in wild-type mice OVA exposure and challenge significantly enhanced SeV-induced airway hyperreactivity and mucous cell metaplasia, but this failed to occur in either Fc?RI?(-/-) or IgE(-/-) mice.

Conclusion

A single exposure to a bystander allergen during a paramyxoviral infection is sufficient to drive allergen specific IgE production in a partial Fc?RI-dependent mechanism. These data begin to provide mechanistic insight into how viral infections might drive development of atopic disease.

SUBMITTER: Cheung DS

PROVIDER: S-EPMC3059126 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Development of atopy by severe paramyxoviral infection in a mouse model.

Cheung Dorothy S DS Ehlenbach Sarah J SJ Kitchens Tom T Riley Desire A DA Grayson Mitchell H MH

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 20101201 6

<h4>Background</h4>Atopic diseases have been increasing in prevalence, yet the initial inciting events that lead to atopy are not understood. Paramyxoviral infections have been suggested to play a role; however, much of these data are correlative.<h4>Objective</h4>To determine whether exposure to a nonviral antigen during a paramyxoviral infection is sufficient to drive IgE production against the bystander antigen and whether clinical disease against this antigen would result.<h4>Methods</h4>Wil ...[more]

PMID: 21130381

Similar Datasets

Project description:BackgroundMicrobial invasion of the intraamniotic cavity and intraamniotic inflammation are factors associated with spontaneous preterm birth. Understanding the route and kinetics of infection, sites of colonization, and mechanisms of host inflammatory response is critical to reducing preterm birth risk.ObjectivesThis study developed an animal model of ascending infection and preterm birth with live bacteria (E. coli) in pregnant CD-1 mice with the goal of better understanding the process of microbial invasion of the intraamniotic cavity and intraamniotic inflammation.Study designMultiple experiments were conducted in this study. To determine the dose of E. coli required to induce preterm birth, CD-1 mice were injected vaginally with four different doses of E. coli (103, 106, 1010, or 1011 colony forming units [CFU]) in 40 μL of nutrient broth or broth alone (control) on an embryonic day (E)15. Preterm birth (defined as delivery before E18.5) was monitored using live video. E. coli ascent kinetics were measured by staining the E. coli with lipophilic tracer DiD for visualization through intact tissue with an in vivo imaging system (IVIS) after inoculation. The E. coli were also directly visualized in reproductive tissues by staining the bacteria with carboxyfluorescein succinimidyl ester (CFSE) prior to administration and via immunohistochemistry (IHC) by staining tissues with anti-E. coli antibody. Each pup's amniotic fluid was cultured separately to determine the extent of microbial invasion of the intraamniotic cavity at different time points. Intraamniotic inflammation resulting from E. coli invasion was assessed with IHC for inflammatory markers (TLR-4, P-NF-κB) and neutrophil marker (Ly-6G) for chorioamnionitis at 6- and 24-h post-inoculation.ResultsVaginally administered E. coli resulted in preterm birth in a dose-dependent manner with higher doses causing earlier births. In ex vivo imaging and IHC detected uterine horns proximal to the cervix had increased E. coli compared to the distal uterine horns. E. coli were detected in the uterus, fetal membranes (FM), and placenta in a time-dependent manner with 6 hr having increased intensity of E. coli positive signals in pups near the cervix and in all pups at 24 hr. Similarly, E. coli grew from the cultures of amniotic fluid collected nearest to the cervix, but not from the more distal samples at 6 hr post-inoculation. At 24 hr, all amniotic fluid cultures regardless of distance from the cervix, were positive for E. coli. TLR-4 and P-NF-κB signals were more intense in the tissues where E. coli was present (placenta, FM and uterus), displaying a similar trend toward increased signal in proximal gestational sacs compared to distal at 6 hr. Ly-6G+ cells, used to confirm chorioamnionitis, were increased at 24 hr compared to 6 hr post-inoculation and control.ConclusionWe report the development of mouse model of ascending infection and the associated inflammation of preterm birth. Clinically, these models can help to understand mechanisms of infection associated preterm birth, determine targets for intervention, or identify potential biomarkers that can predict a high-risk pregnancy status early in pregnancy.

Project description:Background & Aims:HDV infection induces the most severe form of human viral hepatitis. However, the specific reasons for the severity of the disease remain unknown. Recently, we developed an HDV replication mouse model in which, for the first time, liver damage was detected. Methods:HDV and HBV replication-competent genomes and HDV antigens were delivered to mouse hepatocytes using adeno-associated vectors (AAVs). Aminotransferase elevation, liver histopathology, and hepatocyte death were evaluated and the immune infiltrate was characterized. Liver transcriptomic analysis was performed. Mice deficient for different cellular and molecular components of the immune system, as well as depletion and inhibition studies, were employed to elucidate the causes of HDV-mediated liver damage. Results:AAV-mediated HBV/HDV coinfection caused hepatocyte necrosis and apoptosis. Activated T lymphocytes, natural killer cells, and proinflammatory macrophages accounted for the majority of the inflammatory infiltrate. However, depletion studies and the use of different knockout mice indicated that neither T cells, natural killer cells nor macrophages were necessary for HDV-induced liver damage. Transcriptomic analysis revealed a strong activation of type I and II interferon (IFN) and tumor necrosis factor (TNF)-? pathways in HBV/HDV-coinfected mice. While the absence of IFN signaling had no effect, the use of a TNF-? antagonist resulted in a significant reduction of HDV-associated liver injury. Furthermore, hepatic expression of HDAg resulted in the induction of severe liver damage, which was T cell- and TNF-?-independent. Conclusions:Both host (TNF-?) and viral (HDV antigens) factors play a relevant role in HDV-induced liver damage. Importantly, pharmacological inhibition of TNF-? may offer an attractive strategy to aid control of HDV-induced acute liver damage. Lay summary:Chronic hepatitis delta constitutes the most severe form of viral hepatitis. There is limited data on the mechanism involved in hepatitis delta virus (HDV)-induced liver pathology. Our data indicate that a cytokine (TNF-?) and HDV antigens play a relevant role in HDV-induced liver damage.

Dataset Information

Development of atopy by severe paramyxoviral infection in a mouse model.

Background

Objective

Methods

Results

Conclusion

Publications

Development of atopy by severe paramyxoviral infection in a mouse model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure