INHIBITION OF TLR4 AND NLRP3 LEADS TO THE EXACERBATION OF IGE SPECIFIC ANTIBODIES IN MOUSE ALLERGIC MODELS BASED ON SUBCUTANEOUS OR INTRANASAL IMMUNIZATION RESPECTIVELY
- Authors: Chudakov D.B.1, Shustova O.A.1, Konovalova M.V.1, Velichinskii R.A.1, Fattakhova G.V.1
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Affiliations:
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, RAS
- Section: Joint Immunology Forum 2024
- URL: https://rusimmun.ru/jour/article/view/16617
- DOI: https://doi.org/10.46235/1028-7221-16617-IOT
- ID: 16617
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Abstract
Abstract
Introduction. Significant increase of the prevalence of the diseases linked with IgE production can be seen in the recent years. But the question about the role of TLR receptors in this process remains controversial. According to the hygiene hypothesis the decrease of the contact of the individual with pathogens that contain PRR receptor ligands in the recent years leads to the development of allergic diseases. The aim of this work was to investigate whether the TLR4 and NLRP3 receptors activation contributes to the allergen-specific antibodies formation. Methods. BALB/c mice were immunized according to two different protocols. In the first one OVA antigen was administered in 0,1 µg dose 2-3 times a week for 6 weeks by subcutaneous route. In the second one OVA was administered in 0,3 µg dose intranasally in combination with 4 ng of benzo(a)pyrene (BaP) 2 times a week for 8 weeks. In both cases TLR4 and NLRP3 receptor inhibitors, namely TLR4-IN-C34 in 1 mg/kg dose and CY-09 in 20 mg/kg dose respectively were also administered to the some of the mice. Specific antibody production was determined by ELISA. Results. Immunization of mice with TLR4-IN-C34 significantly (p<0.01) amplify IgE production (about 2,5 times in comparison with control group) but has no effect on specific IgG1 production in subcutaneous model. Specific IgE titers in the control group immunized without small molecule inhibitor and in the TLR4-IN-C34 group were (3±0.6)*103 and (8±2)*103 respectively. In this model CY-09 administration has no effect on humoral immune response. In the secondary (intranasal) model BaP significantly increase specific IgE and IgG1 production. CY-09 but not TLR4-IN-C34 administered in combination with BaP significant (p<0.05) and approximately 2 times enhances specific IgE but not IgG1 production. Specific IgE titers in the control group without inhibitor and in the CY-09 group were (2,0±0,4)*102 and (5,1±0,3)*102 respectively. Conclusion. So, PRR-activation, in our case activation of TLR4 in the model based on subcutaneous immunization or NLRP3 in the model based on intranasal antigen administration with BaP suppressed the production of allergen-specific IgE but not IgG1. These data are in consistend with hygiene theory of allergy development.
Keywords
About the authors
Dmitrii Borisovich Chudakov
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, RAS
Email: boris-chudakov@yandex.ru
ORCID iD: 0000-0003-2143-9824
SPIN-code: 1083-5876
Scopus Author ID: 57190496716
ResearcherId: AAE-2775-2019
PhD, Research assistant, Laboratory of Cell interactions
Russian Federation, 117997, Russia, Moscow, Miklukho-Maklaya St. 16/10Olga Alexandrovna Shustova
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, RAS
Author for correspondence.
Email: olga_shustova@list.ru
ORCID iD: 0000-0002-2330-7326
SPIN-code: 9571-4667
Scopus Author ID: 57191161776
PhD, junior researcher, Laboratory of Cell Interactions
Russian Federation, 117997, Russia, Moscow, Miklukho-Maklaya St. 16/10Mariya Vladimirovna Konovalova
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, RAS
Email: mariya.v.konovalova@gmail.com
ORCID iD: 0000-0002-9174-1896
SPIN-code: 4888-4006
Scopus Author ID: 36196735900
PhD, research assistant, Laboratory of Cell Interactions
Russian Federation, 117997, Russia, Moscow, Miklukho-Maklaya St. 16/10Rodion Albertovich Velichinskii
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, RAS
Email: rodicvelic@gmail.com
SPIN-code: 5338-7085
Scopus Author ID: 57210576106
Research engineer, Laboratory of Cell Interactions
Russian Federation, 117997, Russia, Moscow, Miklukho-Maklaya St. 16/10Gulnar Vaisovna Fattakhova
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, RAS
Email: fattakhova@yahoo.com
ORCID iD: 0000-0002-3158-7946
Scopus Author ID: 36081735000
PhD, research assistant, Laboratory of Cell Interactions
Russian Federation, 117997, Russia, Moscow, Miklukho-Maklaya St. 16/10References
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