The role of innate immunity in the development of chronic rhinosinusitis and perspectives of its conservative management
- Authors: Egorov V.I.1, Savlevich E.L.2
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Affiliations:
- Moscow Regional Research and Clinical Institute (MONIKI), Moscow
- Central State Medical Academy of Department for Presidential Affairs of the Russian Federation, Moscow
- Issue: Vol 44, No 7 (2016)
- Pages: 850-856
- Section: LECTURE
- URL: https://almclinmed.ru/jour/article/view/394
- DOI: https://doi.org/10.18786/2072-0505-2016-44-7-850-856
- ID: 394
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Abstract
Chronic rhinosinusitis (CRS) is a heterogeneous, multifactorial disease of unknown etiology, with an underlying deficient immune response to infectious and other triggers, leading to their incomplete elimination and persistence of inflammation. Development of CRS is made possible by a deficient response of the innate immunity of nasal and paranasal sinus mucosa. The main factors of non-specific defense system of nasal and paranasal mucosa are the function of cell junctions between epithelial cells, mucociliary clearance, pattern recognition receptors (PRRs), antigen presenting cells, and phagocytosis. The multirowed ciliate epithelium of nasal and paranasal sinus mucosa is covered by a thick layer of mucus containing more than 200 proteins. Changes in the qualitative composition of the nasal mucus in CRS manifests in overexpression of the main mucins MUC5AC and MUC5B and decreased synthesis of lactoferrin and lyzocin. Ciliary dyskinesia or abnormalities in their microstructure lead to decreased efficacy of mucociliary clearance. Diminished expression of proteins of tight junctions (TJ) ZO-1 and occluding results in decreased density of intercellular contacts and increased permeability of epithelial barrier. In addition, CRS is characterized by deficient Tolllike receptors (TLR) 9, 2 and 4, as well as increased counts of M2 macrophages in the mucosa. This results in suppressed phagocytosis and antimicrobial mucosal defense. Lower levels of STAT3 protein causes an imbalanced reaction of innate and adaptive immune response and disordered reparation processes. With abnormal functioning of all the above mentioned mechanisms, no immune elimination of infectious agents can take place, with increased susceptibility to viral and bacterial infections of the upper respiratory tract. This opens the door to development of CRS, including that with polyps. Investigation of the innate immunity factors would allow for predicting of inflammation in a given patient, as well as for development of new approaches to its conservative management.
About the authors
V. I. Egorov
Moscow Regional Research and Clinical Institute (MONIKI), Moscow
Email: fake@neicon.ru
Egorov Viktor I. - MD, PhD, Head of Department of Otorhinolaryngology; Head of Chair of Otorhinolaryngology, Postgraduate Training Faculty
РоссияE. L. Savlevich
Central State Medical Academy of Department for Presidential Affairs of the Russian Federation, Moscow
Author for correspondence.
Email: savllena@gmail.com
Savlevich Elena L. - MD, PhD, Associate Professor, Chair of Otorhinolaryngology.
19-1А Marshala Timoshenko ul., Moscow, 121359, Russian Federation. Tel.: +7 (985) 145 27 45. E-mail: savllena@gmail.com РоссияReferences
- Akdis CA, Bachert C, Cingi C, Dykewicz MS, Hellings PW, Naclerio RM, Schleimer RP, Ledford D. Endotypes and phenotypes of chronic rhinosinusitis: a PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol. 2013;131(6):1479-90. doi: 10.1016/j.jaci.2013.02.036.
- Smith KA, Orlandi RR, Rudmik L. Cost of adult chronic rhinosinusitis: A systematic review. Laryngoscope. 2015;125(7):1547-56. doi: 10.1002/lary.25180.
- Van Crombruggen K, Zhang N, Gevaert P, To-massen P, Bachert C. Pathogenesis of chronic rhinosinusitis: inflammation. J Allergy Clin Immunol. 2011;128(4):728-32. doi: 10.1016/j.jaci.2011.07.049.
- Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alo-bid I, Baroody F, Cohen N, Cervin A, Douglas R, Gevaert P, Georgalas C, Goossens H, Harvey R, Hellings P, Hopkins C, Jones N, Joos G, Ka-logjera L, Kern B, Kowalski M, Price D, Riech-elmann H, Schlosser R, Senior B, Thomas M, Toskala E, Voegels R, Wang de Y, Wormald PJ. European Position Paper on Rhinosinusitis and Nasal Polyps 2012. Rhinol Suppl. 2012;50(23):1-298.
- Козлов ВС, Савлевич ЕЛ. Полипозный рино-синусит. Современные подходы к изучению патогенеза, диагностике и лечению. Вестник оториноларингологии. 2015;80(4):95-9.
- Harkema JR, Carey SA, Wagner JG. The nose revisited: a brief review of the comparative structure, function, and toxicologic pathology of the nasal epithelium. Toxicol Pathol. 2006;34(3):252-69. doi: 10.1080/01926230600713475.
- Tieu DD, Kern RC, Schleimer RP. Alterations in epithelial barrier function and host defense responses in chronic rhinosinusitis. J Allergy Clin Immunol. 2009;124(1):37-42. doi: 10.1016/j.jaci.2009.04.045.
- Bachert C, Pawankar R, Zhang L, Bunnag C, Fokkens WJ, Hamilos DL, Jirapongsananuruk O, Kern R, Meltzer EO, Mullol J, Naclerio R, Pilan R, Rhee CS, Suzaki H, Voegels R, Blaiss M. ICON: chronic rhinosinusitis. World Allergy Organ J. 2014;7(1):25. doi: 10.1186/1939-4551-7-25.
- Toppila-Salmi S, van Drunen CM, Fokkens WJ, Golebski K, Mattila P, Joenvaara S, Renkonen J, Renkonen R. Molecular mechanisms of nasal epithelium in rhinitis and rhinosinusitis. Curr Allergy Asthma Rep. 2015;15(2):495. doi: 10.1007/s11882-014-0495-8.
- Bingle CD, Craven CJ. PLUNC: a novel family of candidate host defence proteins expressed in the upper airways and nasopharynx. Hum Mol Genet. 2002;11(8):937-43. doi: 10.1093/hmg/11.8.937.
- Молдавская АА, Храппо НС, Левитан БН, Петров ВВ. Особенности организации слизистой оболочки и сосудистой системы полости носа: морфо-функциональные и клинические аспекты. Успехи современного естествознания. 2006;(5):18-22.
- Donovan BY, Lid ВW, Hua M. Mucociliary dysfunction: real and potential pathogenic mechanisms in mucus, ciliary activity and mucociliary interaction. Pediatr Pulmonol. 1997;23 Suppl 14 :108.
- Demarco RC, Tamashiro E, Rossato M, Ferreira MD, Valera FC, Anselmo-Lima WT. Ciliary ultrastructure in patients with chronic rhinosi-nusitis and primary ciliary dyskinesia. Eur Arch Otorhinolaryngol. 2013;270(7):2065-70. doi: 10.1007/s00405-012-2342-7.
- Mao YJ, Chen HH, Wang B, Liu X, Xiong GY. Increased expression of MUC5AC and MUC5B promoting bacterial biofilm formation in chronic rhinosinusitis patients. Auris Na-sus Larynx. 2015;42(4):294-8. doi: 10.1016/j.anl.2014.12.004.
- Psaltis AJ, Bruhn MA, Ooi EH, Tan LW, Wormald PJ. Nasal mucosa expression of lac-toferrin in patients with chronic rhinosinusitis. Laryngoscope. 2007;117(11):2030-5. doi: 10.1097/MLG.0b013e31812e01ab.
- Ooi EH, Wormald PJ, Tan LW. Innate immunity in the paranasal sinuses: a review of nasal host defenses. Am J Rhinol. 2008;22(1):13-9. doi: 10.2500/ajr.2008.22.3127.
- Seshadri S, Lin DC, Rosati M, Carter RG, Norton JE, Suh L, Kato A, Chandra RK, Harris KE, Chu HW, Peters AT, Tan BK, Conley DB, Gram-mer LC, Kern RC, Schleimer RP. Reduced expression of antimicrobial PLUNC proteins in nasal polyp tissues of patients with chronic rhinosinusitis. Allergy. 2012;67(7):920-8. doi: 10.1111/j.1398-9995.2012.02848.x.
- Tieu DD, Peters AT, Carter RG, Suh L, Conley DB, Chandra R, Norton J, Grammer LC, Harris KE, Kato A, Kern RC, Schleimer RP. Evidence for diminished levels of epithelial psoriasin and cal-protectin in chronic rhinosinusitis. J Allergy Clin Immunol. 2010;125(3):667-75. doi: 10.1016/j.jaci.2009.11.045.
- Li Y, Wang X, Wang R, Bo M, Fan E, Duan S, Zhang L. The expression of epithelial intercellular junctional proteins in the sin-onasal tissue of subjects with chronic rhi-nosinusitis: a histopathologic study. ORL J Otorhinolaryngol Relat Spec. 2014;76(2):110-9. doi: 10.1159/000362246.
- Soyka MB, Wawrzyniak P, Eiwegger T, Holzmann D, Treis A, Wanke K, Kast JI, Ak-dis CA. Defective epithelial barrier in chronic rhinosinusitis: the regulation of tight junctions by IFN-y and IL-4. J Allergy Clin Immunol. 2012;130(5):1087-1096.e10. doi: 10.1016/j.jaci.2012.05.052.
- Steelant B, Farre R, Wawrzyniak P, Belmans J, Dekimpe E, Vanheel H, Van Gerven L, Kortekaas Krohn I, Bullens DM, Ceuppens JL, Akdis CA, Boeckxstaens G, Seys SF, Hellings PW. Impaired barrier function in patients with house dust mite-induced allergic rhinitis is accompanied by decreased occludin and zonula occludens-1 expression. J Allergy Clin Immu-854 Лекция nol. 2016;137(4):1043-53.e1-5. doi: 10.1016/j.jaci.2015.10.050.
- Mansson A, Bogefors J, Cervin A, Uddman R, Cardell LO. NOD-like receptors in the human upper airways: a potential role in nasal polyposis. Allergy. 2011;66(5):621-8. doi: 10.1111/j.13989995.2010.02527.x.
- Tengroth L, Arebro J, Kumlien Georen S, Win-qvist O, Cardell LO. Deprived TLR9 expression in apparently healthy nasal mucosa might trigger polyp-growth in chronic rhinosinusitis patients. PLoS One. 2014;9(8):e105618. doi: 10.1371/journal.pone.0105618.
- Wang X, Zhao C, Ji W, Xu Y, Guo H. Relationship of TLR2, TLR4 and tissue remodeling in chronic rhinosinusitis. Int J Clin Exp Pathol. 2015;8(2):1199-212.
- Wang N, Liang H, Zen K. Molecular mechanisms that influence the macrophage m1-m2 polarization balance. Front Immunol. 2014;5:614. doi: 10.3389/fimmu.2014.00614.
- Krysko O, Holtappels G, Zhang N, Kubica M, Deswarte K, Derycke L, Claeys S, Hammad H, Brusselle GG, Vandenabeele P, Krysko DV, Bach-ert C. Alternatively activated macrophages and impaired phagocytosis of S. aureus in chronic rhinosinusitis. Allergy. 2011;66(3):396-403. doi: 10.1111/j.1398-9995.2010.02498.x.
- Hulse KE, Chaung K, Seshadri S, Suh L, Norton JE, Carter RG, Kern RC, Conley DB, Chandra RK, Tan BK, Peters AT, Grammer LC 3rd, Harris KE, Torgerson TR, Kato A, Schleimer RP. Suppressor of cytokine signaling 3 expression is diminished in sinonasal tissues from patients with chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol. 2014;133(1):275-7.e1. doi: 10.1016/j.jaci.2013.08.015.
- Kupper DS, Valera FC, Malinsky R, Milanezi CM, Silva JS, Tamashiro E, Anselmo-Lima WT. Expression of apoptosis mediators p53 and caspase 3, 7, and 9 in chronic rhinosinusitis with nasal polyposis. Am J Rhinol Allergy. 2014;28(3):187-91. doi: 10.2500/ajra.2014.28.4022.
- De Schryver E, Calus L, van Zele T, Bachert C, Gevaert P. Comparison of different medical treatment options for CRSwNP: doxycycline, methylprednisolone, mepolizumab and omal-izumab. Clin Transl Allergy. 2015;5 Suppl 4:P41. doi: 10.1186/2045-7022-5-S4-P41.
- Kato A. Immunopathology of chronic rhinosinusitis. Allergol Int. 2015;64(2):121-30. doi: 10.1016/j.alit.2014.12.006.