Advertisement

Regulation of Type 2 Immunity by Basophils

  • David VoehringerEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 785)

Abstract

The immune response against helminths and allergens is generally characterized by high levels of IgE and increased numbers of Th2 cells, eosinophils, and basophils. Basophils represent a relatively rare population of effector cells and their in vivo functions are incompletely understood. Recent studies with basophil-depleting antibodies revealed that these cells might play an important role during the early and late stages of type 2 immune responses. To further characterize the relevance of basophils for protective immunity and orchestration of allergic inflammation, we generated constitutively basophil-deficient mice. We observed a normal Th2 response induced by helminth infections or immunization with alum/OVA or papain/OVA. However, basophils contributed to worm expulsion during secondary helminth infection and mediated an IgE-dependent inflammatory response of the skin. These results argue against a critical role of basophils as antigen-presenting cells for induction of Th2 polarization and highlight their effector cell potential during later stages of a type 2 immune response.

Keywords

Helminths Allergy IgE Th2 cells 

Notes

Acknowledgment

This work was supported by an ERC starting grant (PAS_241506) from the European Union FP7.

References

  1. 1.
    Iwasaki H, Mizuno S, Arinobu Y, et al. The order of expression of transcription factors directs hierarchical specification of hematopoietic lineages. Genes Dev 2006; 20(21):3010–21.PubMedCrossRefGoogle Scholar
  2. 2.
    Ohnmacht C, Voehringer D. Basophil effector function and homeostasis during helminth infection. Blood 2009; 113(12):2816–25.PubMedCrossRefGoogle Scholar
  3. 3.
    Shen T, Kim S, Do JS, Wang L, Lantz C, Urban JF, Le Gros G, Min B. T cell-derived IL-3 plays key role in parasite infection-induced basophil production but is dispensable for in vivo basophil survival. Int Immunol 2008; 20(9):1201–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Kim S, Prout M, Ramshaw H, Lopez AF, LeGros G, Min B. Cutting edge: basophils are transiently recruited into the draining lymph nodes during helminth infection via IL-3, but infection-induced Th2 immunity can develop without basophil lymph node recruitment or IL-3. J Immunol 2010; 184(3):1143–7.PubMedCrossRefGoogle Scholar
  5. 5.
    Siracusa MC, Saenz SA, Hill DA, et al. TSLP promotes interleukin-3-independent basophil haematopoiesis and type 2 inflammation. Nature 2011; 477(7363):229–33.PubMedCrossRefGoogle Scholar
  6. 6.
    Hida S, Tadachi M, Saito T, Taki S. Negative control of basophil expansion by IRF-2 critical for the regulation of Th1/Th2 balance. Blood 2005; 106(6):2011–7.PubMedCrossRefGoogle Scholar
  7. 7.
    Charles N, Watford WT, Ramos HL, et al. Lyn kinase controls basophil GATA-3 transcription factor expression and induction of Th2 cell differentiation. Immunity 2009; 30(4):533–43.PubMedCrossRefGoogle Scholar
  8. 8.
    Oh K, Shen T, Le Gros G, Min B. Induction of Th2 type immunity in a mouse system reveals a novel immunoregulatory role of basophils. Blood 2007; 109(7):2921–7.PubMedGoogle Scholar
  9. 9.
    Sokol CL, Barton GM, Farr AG, Medzhitov R. A mechanism for the initiation of allergen-induced T helper type 2 responses. Nat Immunol 2008; 9(3):310–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Sokol CL, Chu NQ, Yu S, Nish SA, Laufer TM, Medzhitov R. Basophils function as antigen-presenting cells for an allergen-induced T helper type 2 response. Nat Immunol 2009; 10(7):713–20.PubMedCrossRefGoogle Scholar
  11. 11.
    Perrigoue JG, Saenz SA, Siracusa MC, et al. MHC class II-dependent basophil-CD4+ T cell interactions promote T(H)2 cytokine-dependent immunity. Nat Immunol 2009; 10(7):697–705.PubMedCrossRefGoogle Scholar
  12. 12.
    Tang H, Cao W, Kasturi SP, et al. The T helper type 2 response to cysteine proteases requires dendritic cell-basophil cooperation via ROS-mediated signaling. Nat Immunol 2010; 11(7):608–17.PubMedCrossRefGoogle Scholar
  13. 13.
    Hammad H, Plantinga M, Deswarte K, Pouliot P, Willart MA, Kool M, Muskens F, Lambrecht BN. Inflammatory dendritic cells–not basophils–are necessary and sufficient for induction of Th2 immunity to inhaled house dust mite allergen. J Exp Med 2010; 207(10):2097–111.PubMedCrossRefGoogle Scholar
  14. 14.
    Phythian-Adams AT, Cook PC, Lundie RJ, et al. CD11c depletion severely disrupts Th2 induction and development in vivo. J Exp Med 2010; 207(10):2089–96.PubMedCrossRefGoogle Scholar
  15. 15.
    Ohnmacht C, Schwartz C, Panzer M, Schiedewitz I, Naumann R, Voehringer D. Basophils orchestrate chronic allergic dermatitis and protective immunity against helminths. Immunity 2010; 33(3):364–74.PubMedCrossRefGoogle Scholar
  16. 16.
    Sullivan BM, Liang HE, Bando JK, Wu D, Cheng LE, McKerrow JK, Allen CD, Locksley RM. Genetic analysis of basophil function in vivo. Nat Immunol 2011; 12(6):527–35.PubMedCrossRefGoogle Scholar
  17. 17.
    Khodoun MV, Orekhova T, Potter C, Morris S, Finkelman FD. Basophils initiate IL-4 production during a memory T-dependent response. J Exp Med 2004; 200(7):857–70.PubMedCrossRefGoogle Scholar
  18. 18.
    Iliopoulos O, Baroody FM, Naclerio RM, Bochner BS, Kagey-Sobotka A, Lichtenstein LM. Histamine-containing cells obtained from the nose hours after antigen challenge have functional and phenotypic characteristics of basophils. J Immunol 1992; 148(7):2223–8.PubMedGoogle Scholar
  19. 19.
    Macfarlane AJ, Kon OM, Smith SJ, et al. Basophils, eosinophils, and mast cells in atopic and nonatopic asthma and in late-phase allergic reactions in the lung and skin. J Allergy Clin Immunol 2000; 105(1 Pt 1):99–107.PubMedCrossRefGoogle Scholar
  20. 20.
    Koshino T, Teshima S, Fukushima N, et al. Identification of basophils by immunohistochemistry in the airways of post-mortem cases of fatal asthma. Clin Exp Allergy 1993; 23(11):919–25.PubMedCrossRefGoogle Scholar
  21. 21.
    Bascom R, Wachs M, Naclerio RM, Pipkorn U, Galli SJ, Lichtenstein LM. Basophil influx occurs after nasal antigen challenge: effects of topical corticosteroid pretreatment. J Allergy Clin Immunol 1988; 81(3):580–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Ito Y, Satoh T, Takayama K, Miyagishi C, Walls AF, Yokozeki H. Basophil recruitment and activation in inflammatory skin diseases. Allergy 2011; 66(8):1107–13.PubMedCrossRefGoogle Scholar
  23. 23.
    Wada T, Ishiwata K, Koseki H, et al. Selective ablation of basophils in mice reveals their nonredundant role in acquired immunity against ticks. J Clin Invest 2010; 120(8):2867–75.PubMedCrossRefGoogle Scholar
  24. 24.
    Mukai K, Matsuoka K, Taya C, et al. Basophils play a critical role in the development of IgE-mediated chronic allergic inflammation independently of T cells and mast cells. Immunity 2005; 23(2):191–202.PubMedCrossRefGoogle Scholar
  25. 25.
    Tsujimura Y, Obata K, Mukai K, et al. Basophils play a pivotal role in immunoglobulin-G-mediated but not immunoglobulin-E-mediated systemic anaphylaxis. Immunity 2008; 28(4):581–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Khodoun M, Strait R, Orekov T, Hogan S, Karasuyama H, Herbert DR, Kohl J, Finkelman FD. Peanuts can contribute to anaphylactic shock by activating complement. The Journal of allergy and clinical immunology 2009; 123(2):342–51.PubMedCrossRefGoogle Scholar
  27. 27.
    Jonsson F, Mancardi DA, Kita Y, et al. Mouse and human neutrophils induce anaphylaxis. J Clin Invest 2011; 121(4):1484–96.PubMedCrossRefGoogle Scholar
  28. 28.
    Wikel SK. Host immunity to ticks. Annu Rev Entomol 1996; 41:1–22.PubMedCrossRefGoogle Scholar
  29. 29.
    Allen JR. Tick resistance: basophils in skin reactions of resistant guinea pigs. Int J Parasitol 1973; 3(2):195–200.PubMedCrossRefGoogle Scholar
  30. 30.
    Brown SJ, Galli SJ, Gleich GJ, Askenase PW. Ablation of immunity to Amblyomma americanum by anti-basophil serum: cooperation between basophils and eosinophils in expression of immunity to ectoparasites (ticks) in guinea pigs. Journal of immunology 1982; 129(2):790–6.Google Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Infection biologyUniversitätsklinikum Erlangen and Friedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany

Personalised recommendations