Morphofunctional Analysis of Antigen Uptake Mechanisms Following Sublingual Immunotherapy with Beads in Mice

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2018 Dec 21

PMID 30571699

Authors

Yaser Hosny Ali Elewa

Tatsuya Mizoguchi

Osamu Ichii

Teppei Nakamura

Yasuhiro Kon

Affiliations

Soon will be listed here.

Abstract

Background: Recently, sublingual immunotherapy (SLIT) has been used as a safe and efficient method for the treatment of and immunization against asthma and various allergies. However, the routes of antigen/allergen (particulate antigen) uptake through the mucosa of the oral cavity remain incompletely understood, as do the roles of sex and age in the process. For this purpose, to elucidate the mechanism and efficacy of SLIT among different sexes and ages, microbeads were dripped into the sublingual region to mimic particulate antigen uptake by the sublingual mucosa.

Methods: Twenty microliters of either phosphate buffered saline (PBS) or fluorescently labelled microbeads (latex and silica beads) were placed under the tongue of both male and female C57BL/6 mice at young (3 months) and old (6 months) ages. The lower jaw was examined 30 min after administration, and beads were detected with a fluorescence stereomicroscope. Morphological observations of the mucosa of the fluorescent areas were made with a scanning electron microscope (SEM) and an all-in-one light fluorescence microscope (LM). Fluorescence intensity was compared between both sexes and ages.

Results: Stereomicroscopic observation revealed fluorescent illuminations in three compartments of the sublingual mucosa: the sublingual caruncles (SC), the oral rostral mucosa (OR) and the buccal mucosa (BM). Interestingly, the fluorescence intensity tended to be higher among females than among males in the SC region in particular. However, there were no significant age-related differences. SEM and LM revealed beads in the lumina of both mandibular ducts and sublingual ducts (Sd). Additionally, the apical cytoplasm of some Sd cells contained silica beads. However, there was no specification in the OR mucosa or BM.

Conclusions: This study reveals the major role Sd plays in local immunity via the antigen uptake mechanisms. Furthermore, our data suggest that the efficacy of SLIT in humans could be affected by sex.

References

Marsella R . Tolerability and clinical efficacy of oral immunotherapy with house dust mites in a model of canine atopic dermatitis: a pilot study. Vet Dermatol. 2010; 21(6):566-71. DOI: 10.1111/j.1365-3164.2010.00890.x. View

Hovav A . Dendritic cells of the oral mucosa. Mucosal Immunol. 2013; 7(1):27-37. DOI: 10.1038/mi.2013.42. View

Passalacqua G, Guerra L, Pasquali M, Lombardi C, Canonica G . Efficacy and safety of sublingual immunotherapy. Ann Allergy Asthma Immunol. 2004; 93(1):3-12. DOI: 10.1016/S1081-1206(10)61440-8. View

Hase K, Ohno H . [Epithelial cells as sentinels in mucosal immune barrier]. Nihon Rinsho Meneki Gakkai Kaishi. 2006; 29(1):16-26. DOI: 10.2177/jsci.29.16. View

DeBOER D, Verbrugge M, Morris M . Clinical and immunological responses of dust mite sensitive, atopic dogs to treatment with sublingual immunotherapy (SLIT). Vet Dermatol. 2016; 27(2):82-7e23. DOI: 10.1111/vde.12284. View

Brook I . The bacteriology of salivary gland infections. Oral Maxillofac Surg Clin North Am. 2009; 21(3):269-74. DOI: 10.1016/j.coms.2009.05.001. View

Penagos M, Compalati E, Tarantini F, Baena-Cagnani R, Huerta J, Passalacqua G . Efficacy of sublingual immunotherapy in the treatment of allergic rhinitis in pediatric patients 3 to 18 years of age: a meta-analysis of randomized, placebo-controlled, double-blind trials. Ann Allergy Asthma Immunol. 2006; 97(2):141-8. DOI: 10.1016/S1081-1206(10)60004-X. View

Ott H, Sieber J, Brehler R, Folster-Holst R, Kapp A, Klimek L . Efficacy of grass pollen sublingual immunotherapy for three consecutive seasons and after cessation of treatment: the ECRIT study. Allergy. 2009; 64(9):1394-401. DOI: 10.1111/j.1398-9995.2009.02194.x. View

Jay D, Nadeau K . Immune mechanisms of sublingual immunotherapy. Curr Allergy Asthma Rep. 2014; 14(11):473. DOI: 10.1007/s11882-014-0473-1. View

10.

Dahl R, Kapp A, Colombo G, de Monchy J, Rak S, Emminger W . Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol. 2006; 118(2):434-40. DOI: 10.1016/j.jaci.2006.05.003. View

11.

Zhong C, Yang W, Li Y, Zou L, Deng Z, Liu M . Clinical evaluation for sublingual immunotherapy with Dermatophagoides farinae drops in adult patients with allergic asthma. Ir J Med Sci. 2017; 187(2):441-446. DOI: 10.1007/s11845-017-1685-x. View

12.

Mascarell L, Lombardi V, Louise A, Saint-Lu N, Chabre H, Moussu H . Oral dendritic cells mediate antigen-specific tolerance by stimulating TH1 and regulatory CD4+ T cells. J Allergy Clin Immunol. 2008; 122(3):603-9.e5. DOI: 10.1016/j.jaci.2008.06.034. View

13.

Amano O, Mizobe K, Bando Y, Sakiyama K . Anatomy and histology of rodent and human major salivary glands: -overview of the Japan salivary gland society-sponsored workshop-. Acta Histochem Cytochem. 2012; 45(5):241-50. PMC: 3496860. DOI: 10.1267/ahc.12013. View

14.

Sakurai Y, Nakamura K, Teruya K, Shimada N, Umeda T, Tanaka H . Prevalence and risk factors of allergic rhinitis and cedar pollinosis among Japanese men. Prev Med. 1998; 27(4):617-22. DOI: 10.1006/pmed.1998.0336. View

15.

Townley R, Suliaman F . The mechanism of corticosteroids in treating asthma. Ann Allergy. 1987; 58(1):1-6. View

16.

Dahl R, Kapp A, Colombo G, de Monchy J, Rak S, Emminger W . Sublingual grass allergen tablet immunotherapy provides sustained clinical benefit with progressive immunologic changes over 2 years. J Allergy Clin Immunol. 2007; 121(2):512-518.e2. DOI: 10.1016/j.jaci.2007.10.039. View

17.

Diesel A . Cutaneous Hypersensitivity Dermatoses in the Feline Patient: A Review of Allergic Skin Disease in Cats. Vet Sci. 2017; 4(2). PMC: 5606602. DOI: 10.3390/vetsci4020025. View

18.

Nagler R . Salivary glands and the aging process: mechanistic aspects, health-status and medicinal-efficacy monitoring. Biogerontology. 2004; 5(4):223-33. DOI: 10.1023/B:BGEN.0000038023.36727.50. View

19.

Mascarell L, Rak S, Worm M, Melac M, Soulie S, Lescaille G . Characterization of oral immune cells in birch pollen-allergic patients: impact of the oral allergy syndrome and sublingual allergen immunotherapy on antigen-presenting cells. Allergy. 2015; 70(4):408-19. DOI: 10.1111/all.12576. View

20.

Pfaffe T, Cooper-White J, Beyerlein P, Kostner K, Punyadeera C . Diagnostic potential of saliva: current state and future applications. Clin Chem. 2011; 57(5):675-87. DOI: 10.1373/clinchem.2010.153767. View