Pollen allergy and pollen sensitization: a new look at an old subject


Volume 68 • Issue 1 • March 2022, pp. 4-15

Received: 25.02.2022​ | Accepted for publication: 03.03.2022 | ​Publication date: 21.03.2022

ORCID logo N.B. Migachevа

Samara State Medical University

Full text PDF (rus)

Relevance. Allergic diseases associated with hypersensitivity to pollen allergens (pollinosis) are an urgent medical and socio-economic problem due to widespread increase in prevalence, a variety of clinical manifestations and a negative impact on the quality of life. Understanding the mechanisms underlying the initiation of sensitization to plant-derived airborne allergens can become the basis for development innovative strategies for the treatment and prevention of hay fever.

The aim of the review is to analyze and systematize the currently available data on the mechanisms of the initiation of pollen sensitization and the realization of allergy to pollen allergens.


1. Lake IR, Jones NR, Agnew M, Goodess CM, Giorgi F, Hamaoui-Laguel L, et al. Climate change and future pollen allergy in Europe. Environ Health Perspect. 2017; 125(3): 385–391.

2. Goryachkina LA, Drobik OS, Nasunova AYU. Pollinozy: sovremennyj vzglyad na problemu. Vestnik semejnoj mediciny. 2012; 1: 10–6. (InRuss.)

3. Pointner L, Bethanis A, Thaler M, Traidl-Hoffmann C, Gilles S, Ferreira F, Aglas L. Initiating pollen sensitization — complex source, complex mechanisms. Clin Transl Allergy. 2020; 10: 36.

4. Emelina UN, Voroncova OA, Bel’tyukov EK. Analiz aeropalinologicheskogo spektra v g. Ekaterinburge. Allergologia i immunologia v pediatrii. 2021; 4: 42–44. (InRuss.)

5. Balabolkin II. Pollinoz u detej i podrostkov: sovremennye aspekty patogeneza i tendencii v terapii. Allergologia i immunologia v pediatrii. 2020; 3 (62): 6–14. (InRuss.)

6. Treudler R. Simon JC. Pollen-related food allergy: an update. Allergol J Intern. 2017; 26: 273–282.

7. Descotes J, Choquet-Kastylevsky G. Gell and Coombs’s classification: is it still valid? Toxicology. 2001; 158 (1–2): 43–49.

8. Kumar S, Jeong Y, Ashraf MU, Bae YS. Dendritic cell-mediated Th2 immunity and immune disorders. Int J Mol Sci. 2019; 20 (9): 2159.

9. Blumchen K, Kallinich T, Hamelmann E. Interleukin-5: a novel target for asthma therapy. Expert Opin Biol Ther. 2001; 1 (3): 433–453.

10. Seyfizadeh N, Seyfizadeh N, Gharibi T, Babaloo Z. Interleukin-13 as an important cytokine: a review on its roles in some human diseases. Acta Microbiol Immunol Hung. 2015; 62 (4): 341–378.

11. Soyer OU, Akdis M, Ring J, Behrendt H, Crameri R, Lauener R, et al. Mechanisms of peripheral tolerance to allergens. Allergy. 2013; 68 (2): 161–170.

12. Liu AH. Revisiting the hygiene hypothesis for allergy and asthma. J Allergy Clin Immunol. 2015; 136 (4): 860–865.

13. Potaczek DP, Harb H, Michel S, Alhamwe BA, Renz H, Tost J. Epigenetics and allergy: from basic mechanisms to clinical applications. Epigenomics. 2017; 9 (4): 539–571.

14. Mattila P, Joenvaara S, Renkonen J, Toppila-Salmi S, Renkonen R. Allergy as an epithelial barrier disease. Clin Transl Allergy. 2011; 1 (1): 5.

15. Gilles-Stein S, Beck I, Chaker A, Bas M, McIntyre M, Cifuentes L, et al. Pollen derived low molecular compounds enhance the human allergen specific immune response in vivo. Clin Exp Allergy. 2016; 46 (10): 1355–1365.

16. McKenna OE, Posselt G, Briza P, Lackner P, Schmitt AO, Gadermaier G, et al. Multi-approach analysis for the identification of proteases within birch pollen. Int J Mol Sci. 2017; 18 (7): 1433.

17. Mabalirajan U. Possible involvement of protease-mediated neutrophil recruitment and epithelial barrier disruption in ragweed pollen sensitization. Am J Respir Cell Mol Biol. 2017; 56 (2): 271–272.

18. Van Cleemput J, Poelaert KCK, Laval K, Impens F, Van den Broeck W, Gevaert K, et al. Pollens destroy respiratory epithelial cell anchors and drive alphaherpesvirus infection. Sci Rep. 2019; 9 (1): 4787.

19. Lopez-Rodriguez JC, Solis-Fernandez G, Barderas R, Villalba M, Batanero E. Effects of Ole e 1 on Human Bronchial Epithelial Cells Cultured at the Air-Liquid Interface. J Investig Allergol Clin Immunol. 2018; 28 (3): 186–189.

20. Kumamoto J, Tsutsumi M, Goto M, Nagayama M, Denda M. Japanese Cedar (Cryptomeria japonica) pollen allergen induces elevation of intracellular calcium in human keratinocytes and impairs epidermal barrier function of human skin ex vivo. Arch Dermatol Res. 2016; 308 (1): 549–544.

21. Hosoki K, Brasier AR, Kurosky A, Boldogh I, Sur S. Reply: protease plays a role in ragweed pollen-induced neutrophil recruitment and epithelial barrier disruption. Am J Respir Cell Mol Biol. 2017; 56 (2): 272–273.

22. Zhu DD, Zhu XW, Jiang XD, Dong Z. Thymic stromal lymphopoietin expression is increased in nasal epithelial cells of patients with mugwort pollen sensitive-seasonal allergic rhinitis. Chin Med J (Engl). 2009; 122 (19): 2303–2307.

23. Deng R, Chen X, Zhang Y, Bian F, Gao N, Hu J, et al. Short ragweed pollen promotes M2 macrophage polarization via TSLP/TSLPR/OX40L signaling in allergic inflammation. Mucosal Immunol. 2019; 12 (5): 1141–1149.

24. Hosoki K, Redding D, Itazawa T, Chakraborty A, Tapryal N, Qian S, et al. Innate mechanism of pollen- and cat dander-induced oxidative stress and DNA damage in the airways. J Allergy Clin Immunol. 2017; 140 (5): 1436–9. e5.

25. Li J, Zhang L, Chen X, Chen D, Hua X, Bian F, et al. Pollen/TLR4 innate immunity signaling initiates IL-33/ST2/Th2 pathways in allergic inflammation. Sci Rep. 2016; 6: 36150.

26. Akasaki S, Matsushita K, Kato Y, Fukuoka A, Iwasaki N, Nakahira M, et al. Murine allergic rhinitis and nasal Th2 activation are mediated via TSLP- and IL-33-signaling pathways. Int Immunol. 2016; 28 (2): 65–76.

27. Mjosberg JM, Trifari S, Crellin NK, Peters CP, van Drunen CM, Piet B, et al. Human IL-25- and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161. Nat Immunol. 2011; 12 (11): 1055–1062.

28. Kouzaki H, Kikuoka H, Matsumoto K, Kato T, Tojima I, Shimizu S, et al. A mechanism of interleukin-25 production from airway epithelial cells induced by Japanese cedar pollen. Clin Immunol. 2018; 193: 46–51.

29. Barlow JL, Peel S, Fox J, Panova V, Hardman CS, Camelo A, et al. IL-33 is more potent than IL-25 in provoking IL-13-producing nuocytes (type 2 innate lymphoid cells) and airway contraction. J Allergy Clin Immunol. 2013; 132 (4): 933–941.

30. Kumar S, Adhikari A. Dose-dependent immunomodulating effects of endotoxin in allergic airway inflammation. Innate Immun. 2017; 23 (3): 249–257.

31. Velasco G, Campo M, Manrique OJ, Bellou A, He H, Arestides RS, et al. Toll-like receptor 4 or 2 agonists decrease allergic inflammation. Am J Respir Cell Mol Biol. 2005; 32 (3): 218–224.

32. Dittrich AM, Chen HC, Xu L, Ranney P, Connolly S, Yarovinsky TO, et al. A new mechanism for inhalational priming: IL-4 bypasses innate immune signals. J Immunol. 2008; 181 (10): 7307–7315.

33. Yang D, Han Z, Oppenheim JJ. Alarmins and immunity. Immunol Rev. 2017; 280 (1): 41–56.

34. Leon B, Ballesteros-Tato A, Browning JL, Dunn R, Randall TD, Lund FE. Regulation of T(H)2 development by CXCR5+ dendritic cells and lymphotoxin-expressing B cells. Nat Immunol. 2012; 13 (7): 681–690.

35. Han M, Hu R, Ma J, Zhang B, Chen C, Li H, et al. Fas signaling in dendritic cells mediates Th2 polarization in HDM-induced allergic pulmonary inflammation. Front Immunol. 2018; 9: 3045.

36. Scheurer S, Toda M, Vieths S. What makes an allergen? Clin Exp Allergy. 2015; 45 (7): 1150–1161.

37. Hsu SC, Chen CH, Tsai SH, Kawasaki H, Hung CH, Chu YT, et al. Functional interaction of common allergens and a C-type lectin receptor, dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN), on human dendritic cells. J Biol Chem. 2010; 285 (11): 7903–7910.

38. Groeme R, Airouche S, Kopecny D, Jaekel J, Savko M, Berjont N, et al. Structural and functional characterization of the major allergen Amb a 11 from short ragweed pollen. J Biol Chem. 2016; 291 (25): 13076–13087.

39. Aglas L, Gilles S, Bauer R, Huber S, Araujo GR, Mueller G, et al. Context matters: Th2 polarization resulting from pollen composition and not from protein-intrinsic allergenicity. J Allergy Clin Immunol. 2018; 142 (3): 984–987.

40. Araujo GR, Aglas L, Vaz ER, Machado Y, Huber S, Himly M, et al. TGFbeta1 mimetic peptide modulates immune response to grass pollen allergens in mice. Allergy. 2020; 75 (4): 882–891.

41. Wimmer M, Alessandrini F, Gilles S, Frank U, Oeder S, Hauser M, et al. Pollen-derived adenosine is a necessary cofactor for ragweed allergy. Allergy. 2015; 70 (8): 944–954.

42. Wolf M, Twaroch TE, Huber S, Reithofer M, Steiner M, Aglas L, et al. Amb a 1 isoforms: unequal siblings with distinct immunological features. Allergy. 2017; 72 (12): 1874–1882.

43. Eisenbarth SC, Zhadkevich A, Ranney P, Herrick CA, Bottomly K. IL-4-dependent Th2 collateral priming to inhaled antigens independent of toll-like receptor 4 and myeloid differentiation factor 88. J Immunol. 2004; 172 (7): 4527–4534.

44. Soh WT, Aglas L, Mueller GA, Gilles S, Weiss R, Scheiblhofer S, et al. Multiple roles of Bet v 1 ligands in allergen stabilization and modulation of endosomal protease activity. Allergy. 2019; 74 (12): 2382–2393.

45. Gilles S, Behrendt H, Ring J, Traidl-Hoffmann C. The pollen enigma: modulation of the allergic immune response by non-allergenic, pollenderived compounds. Curr Pharm Des. 2012; 18 (16): 2314–2319.

46. Chruszcz M, Chew FT, Hoffmann-Sommergruber K, Hurlburt BK, Mueller GA, Pomés A et al. Allergens and their associated small molecule ligands-their dual role in sensitization. Allergy. 2021; 76 (8): 2367–2382.

47. Gisler A. Allergies in Urban Areas on the Rise: The Combined Effect of Air Pollution and Pollen. Int J Public Health. 2021; 66: 1604022.

48. Bublin M, Eiwegger T, Breiteneder H. Do lipids influence the allergic sensitization process? J Allergy Clin Immunol. 2014; 134 (3): 521–529.

49. Agea E, Russano A, Bistoni O, Mannucci R, Nicoletti I, Corazzi L, et al. Human CD1-restricted T cell recognition of lipids from pollens. J Exp Med. 2005; 202 (2): 295–308.

50. Gilles S, Mariani V, Bryce M, Mueller MJ, Ring J, Behrendt H, et al. Pollen allergens do not come alone: pollen associated lipid mediators (PALMS) shift the human immune systems towards a T(H)2-dominated response. Allergy Asthma Clin Immunol. 2009; 5 (1): 3.

51. Gunawan H, Takai T, Kamijo S, Wang XL, Ikeda S, Okumura K, et al. Characterization of proteases, proteins, and eicosanoid-like substances in soluble extracts from allergenic pollen grains. Int Arch Allergy Immunol. 2008; 147 (4): 276–288.

52. Oeder S, Alessandrini F, Wirz OF, Braun A, Wimmer M, Frank U, et al. Pollen-derived nonallergenic substances enhance Th2-induced IgE production in B cells. Allergy. 2015; 70 (11): 1450–1460.

53. Gilles S, Fekete A, Zhang X, Beck I, Blume C, Ring J, et al. Pollen metabolome analysis reveals adenosine as a major regulator of dendritic cellprimed T(H) cell responses. J Allergy Clin Immunol. 2011; 127 (2): 454–461.

54. Vinhas R, Cortes L, Cardoso I, Mendes VM, Manadas B, Todo-Bom A, et al. Pollen proteases compromise the airway epithelial barrier through degradation of transmembrane adhesion proteins and lung bioactive peptides. Allergy. 2011; 66 (8): 1088–1098.

55. Kheradmand F, Kiss A, Xu J, Lee SH, Kolattukudy PE, Corry DB. A protease-activated pathway underlying Th cell type 2 activation and allergic lung disease. J Immunol. 2002; 169 (10): 5904–5911.

56. Barnes CS. Impact of climate change on pollen and respiratory disease. Curr Allergy Asthma Rep. 2018; 18 (11): 59.

57. Lee P-H, Park S, Lee Y-G, Choi S-M, An M-H, Jang A-S. The Impact of Environmental Pollutants on Barrier Dysfunction in Respiratory Disease. Allergy Asthma Immunol Res. 2021; 13 (6): 850–862.

58. Schiavoni G, D’Amato G, Afferni C. The dangerous liaison between pollens and pollution in respiratory allergy. Ann Allergy Asthma Immunol. 2017; 118 (3): 269–275.

59. Behrendt H, Becker WM. Localization, release and bioavailability of pollen allergens: the influence of environmental factors. Curr Opin Immunol. 2001; 13 (6): 709–15.

60. Beck I, Jochner S, Gilles S, McIntyre M, Buters JT, Schmidt-Weber C, et al. High environmental ozone levels lead to enhanced allergenicity of birch pollen. PLoS ONE. 2013; 8 (11): e80147.

61. Zasloff M. Pollen has a microbiome: implications for plant reproduction, insect pollination and human allergies. Environ Microbiol. 2017; 19 (1): 1–2.

62. Obersteiner A, Gilles S, Frank U, Beck I, Haring F, Ernst D, et al. Pollenassociated microbiome correlates with pollution parameters and the allergenicity of pollen. PLoS ONE. 2016; 11(2): e0149545.

63. Zhu Z, Oh SY, Zheng T, Kim YK. Immunomodulating effects of endotoxin in mouse models of allergic asthma. Clin Exp Allergy. 2010; 40(4): 536–546.

64. Heydenreich B, Bellinghausen I, Konig B, Becker WM, Grabbe S, Petersen A, et al. Gram-positive bacteria on grass pollen exhibit adjuvant activity inducing inflammatory T cell responses. Clin Exp Allergy. 2012; 42(1): 76–84.

65. Pallett DW, Soh E, Edwards ML, Bodey K, Lau LC, Cooper JI, et al. Proof of concept pilot study: prevalence of grass virus infection and the potential for effects on the allergenic potency of pollen. Environ Health. 2009; 8(Suppl 1): S10.

66. Белан ЭБ. Аллерген-специфическая иммунотерапия как метод лечения аллергических заболеваний. Астраханский медицинский журнал. 2018; 1(13): 6–14. [Belan EB. Allergen-specificheskaya immunoterapiya kak metod lecheniya allergicheskih zabolevanij. Astrahanskij medicinskij zhurnal. 2018; 1(13): 6–14. (InRuss.).

67. Pavón-Romero GF, Parra-Vargas MI, Ramírez-Jiménez F, Melgoza-Ruiz E, Serrano-Pérez NH, Teran LM. Allergen Immunotherapy: Current and Future Trends. Cells. 2022; 11 (2): 212.

68. Durham SR, Penagos M. Sublingual or subcutaneous immunotherapy for allergic rhinitis? J Allergy Clin Immunol. 2016; 137 (2): 339–349.

69. Grunlund H, Gafvelin G. Recombinant Bet v 1 vaccine for treatment of allergy to birch pollen. Hum Vaccin. 2010; 6 (12): 970–977.

70. Wang W, Yin J. Is it worthy to take full-course immunotherapy for allergic rhinitis? About efficacy biomarker of allergen immunotherapy. Scand J Immunol. 2020; 91 (1): e12817.


Migacheva NB. Pollen allergy and pollen sensitization: a new look at an old subject. Allergology and Immunology in Pediatrics. 2022;1:4-15. (In Russ.) https://doi.org/10.53529/2500-1175-2022-1-4-15

For correspondence:

Migacheva Natalia Begievna

MD, PhD, Head of Department of Pediatrics, Institution of Professional Education, Samara State Medical University

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Сonflict of interest::

N.B. Migachevа is a member of the editorial board