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Basophil activation through TLR2 and TLR4 signaling pathways

1 INSERM U1016, Institut Cochin, Paris, France
2 CNRS-UMR 8104, Paris, France
3 Université Paris Descartes, 75014 Paris, France
4 CNRS-UMR 8147, Hôpital Necker, 75015 Paris, France
5 Labex inflamex, Paris, France

Basophils are effector cells that respond to protease allergens and parasites, thus contributing to allergic inflammation and Th2 differentiation. However, the molecular interactions through which pathogens promote activation as well as recruitment of these cells to sites of inflammation remain poorly understood. We found that administration of extracts from Nippostrongylus brasiliensis induced both basophil recruitment into blood and liver in vivo and IL-4 and histamine production by purified bone marrow-derived basophils in vitro. Starting from this finding, we set out to identify putative pathogen-derived molecules for their capacity to activate murine basophils, using a basophil population differentiated and expanded from bone marrow cells cultured with IL-3 and sorted as a CD49b+ c-kit subset. Among a number of Toll-like receptor (TLR) agonists tested, we found that the lipopeptide Pam2CSK4 and lipopolysaccharide (LPS) activate basophils in terms of IL-4, IL-6 and histamine production through TLR2 and TLR4, respectively. By contrast, TLR3 or TLR7 agonists had no such effect. We further identified nitric oxide (NO) as key mediator for LPS stimulation and established that in vivo administration of LPS led to basophil recruitment into the liver. Our results reveal the important contribution of MyD88 and NO signaling to antigen recognition through TLR2 and TLR4 pathways leading to activation, degranulation and release of immunoregulatory mediators.
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Keywords basophils; PAMP; IL-4; histamine; TLR

Citation: Manal Alkan, Fadel Sayes, Abdulraouf Ramadan, Francois Machavoine, Michel Dy, Elke Schneider, Nathalie Thieblemont. Basophil activation through TLR2 and TLR4 signaling pathways. AIMS Allergy and Immunology, 2018, 2(3): 126-140. doi: 10.3934/Allergy.2018.3.126


  • 1. Centers for Disease C, Prevention (2011) Vital signs: asthma prevalence, disease characteristics, and self-management education: United States, 2001–2009. MMWR Morb Mortal Wkly Rep 60: 547–552.
  • 2. Karasuyama H, Miyake K, Yoshikawa S, et al. (2017) Multifaceted roles of basophils in health and disease. J Allergy Clin Immun 6749: 31894–31898.
  • 3. Korosec P, Gibbs BF, Rijavec M, et al. (2018) Important and specific role for basophils in acute allergic reactions. Clin Exp Allergy 48: 502–512.    
  • 4. Hashimoto T, Rosen JD, Sanders KM, et al. (2018) Possible roles of basophils in chronic itch. Exp Dermatol, In press.
  • 5. Rosenstein RK, Bezbradica JS, Yu S, et al. (2014) Signaling pathways activated by a protease allergen in basophils. Proc Natl Acad Sci USA 111: E4963–E4971.    
  • 6. Chirumbolo S, Bjorklund G, Sboarina A, et al. (2018) The role of basophils as innate immune regulatory cells in allergy and immunotherapy. Hum Vacc Immunother 14: 815–831.    
  • 7. Lantz CS, Boesiger J, Song CH, et al. (1998) Role for interleukin-3 in mast-cell and basophil development and in immunity to parasites. Nature 392: 90–93.    
  • 8. Le Gros G, Ben-Sasson SZ, Conrad DH, et al. (1990) IL-3 promotes production of IL-4 by splenic non-B, non-T cells in response to Fc receptor cross-linkage. J Immunol 145: 2500–2506.
  • 9. Min B, Prout M, Hu LJ, et al. (2004) Basophils produce IL-4 and accumulate in tissues after infection with a Th2-inducing parasite. J Exp Med 200: 507–517.    
  • 10. Hida S, Yamasaki S, Sakamoto Y, et al. (2009) Fc receptor gamma-chain, a constitutive component of the IL-3 receptor, is required for IL-3-induced IL-4 production in basophils. Nat Immunol 10: 214–222.    
  • 11. Ohmori K, Luo Y, Jia Y, et al. (2009) IL-3 induces basophil expansion in vivo by directing granulocyte-monocyte progenitors to differentiate into basophil lineage-restricted progenitors in the bone marrow and by increasing the number of basophil/mast cell progenitors in the spleen. J Immunol 182: 2835–2841.    
  • 12. Herbst T, Esser J, Prati M, et al. (2012) Antibodies and IL-3 support helminth-induced basophil expansion. Proc Natl Acad Sci USA 109: 14954–14959.    
  • 13. Siracusa MC, Saenz SA, Hill DA, et al. (2011) TSLP promotes interleukin-3-independent basophil haematopoiesis and type 2 inflammation. Nature 477: 229–233.    
  • 14. Schneider E, Petit-Bertron AF, Bricard R, et al. (2009) IL-33 activates unprimed murine basophils directly in vitro and induces their in vivo expansion indirectly by promoting hematopoietic growth factor production. J Immunol 183: 3591–3597.    
  • 15. Varricchi G, Raap U, Rivellese F, et al. (2018) Human mast cells and basophils-How are they similar how are they different? Immunol Rev 282: 8–34.    
  • 16. Ohnmacht C, Voehringer D (2010) Basophils protect against reinfection with hookworms independently of mast cells and memory Th2 cells. J Immunol 184: 344–350.    
  • 17. Kampfer SS, Odermatt A, Dahinden CA, et al. (2017) Late IL-3-induced phenotypic and functional alterations in human basophils require continuous IL-3 receptor signaling. J Leukocyte Biol 101: 227–238.    
  • 18. Reese TA, Liang HE, Tager AM, et al. (2007) Chitin induces accumulation in tissue of innate immune cells associated with allergy. Nature 447: 92–96.    
  • 19. Schneider E, Thieblemont N, De Moraes ML, et al. (2010) Basophils: new players in the cytokine network. Eur Cytokine Netw 21: 142–153.
  • 20. Brown GD, Herre J, Williams DL, et al. (2003) Dectin-1 mediates the biological effects of beta-glucans. J Exp Med 197: 1119–1124.    
  • 21. Ramadan A, Pham VL, Machavoine F, et al. (2013) Activation of basophils by the double-stranded RNA poly(A:U) exacerbates allergic inflammation. Allergy 68: 732–738.    
  • 22. Hill DA, Siracusa MC, Abt MC, et al. (2012) Commensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation. Nat Med 18: 538–546.    
  • 23. Hammad H, Chieppa M, Perros F, et al. (2009) House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells. Nat Med 15: 410–416.    
  • 24. Iwasaki N, Matsushita K, Fukuoka A, et al. (2017) Allergen endotoxins induce T-cell-dependent and non-IgE-mediated nasal hypersensitivity in mice. J Allergy Clin Immun 139: 258–268.e210.    
  • 25. Schroeder JT, Chichester KL, Bieneman AP (2009) Human basophils secrete IL-3: evidence of autocrine priming for phenotypic and functional responses in allergic disease. J Immunol 182: 2432–2438.    
  • 26. Gentinetta T, Pecaric-Petkovic T, Wan D, et al. (2011) Individual IL-3 priming is crucial for consistent in vitro activation of donor basophils in patients with chronic urticaria. J Allergy Clin Immun 128: 1227–1234.e1225.    
  • 27. Bieneman AP, Chichester KL, Chen YH, et al. (2005) Toll-like receptor 2 ligands activate human basophils for both IgE-dependent and IgE-independent secretion. J Allergy Clin Immun 115: 295–301.    
  • 28. Smith TF, Aelvoet M, Morrison DC (1985) The effect of bacterial lipopolysaccharide (LPS) on histamine release from human basophils. I. Enhancement of immunologic release by LPS. Clin Immunol Immunopathol 34: 355–365.
  • 29. Norn S, Baek L, Jensen C, et al. (1986) Influence of bacterial endotoxins on basophil histamine release. Potentiation of antigen- and bacteria-induced histamine release. Allergy 41: 125–130.
  • 30. Schwartz C, Oeser K, Prazeres da CC, et al. (2014) T cell-derived IL-4/IL-13 protects mice against fatal Schistosoma mansoni infection independently of basophils. J Immunol 193: 3590–3599.    
  • 31. Magalhaes K, Almeida PE, Atella G, et al. (2010) Schistosomal-derived lysophosphatidylcholine are involved in eosinophil activation and recruitment through Toll-like receptor-2-dependent mechanisms. J Infect Dis 202: 1369–1379.    
  • 32. Watanabe T, Yamashita K, Sakurai T, et al. (2013) Toll-like receptor activation in basophils contributes to the development of IgG4-related disease. J Gastroenterol 48: 247–253.    
  • 33. Wenceslau CF, McCarthy CG, Szasz T, et al. (2015) Mitochondrial N-formyl peptides induce cardiovascular collapse and sepsis-like syndrome. Am J Physiol-Heart C 308: H768–H777.    
  • 34. Yamanishi Y, Miyake K, Iki M, et al. (2017) Recent advances in understanding basophil-mediated Th2 immune responses. Immunol Rev 278: 237–245.    


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