Basophils in allergic immune responses

https://doi.org/10.1016/j.coi.2011.09.005Get rights and content

Basophils are rare effector cells of the innate immune system. They are generally associated with type 2 immune responses that develop during helminth infections and allergic reactions. The role of basophils for initiation and execution of allergic immune responses is not well understood. Over the past few years new tools have been generated to study the function of basophils in mouse models. Depending on the experimental systems used conflicting results were obtained with regard to the role of basophils for initiation and execution of immune responses against allergens and helminths. This review highlights the current knowledge about basophil in vivo functions with a focus on the role of basophils for allergic responses like asthma, allergic skin diseases and anaphylaxis.

Highlights

Basophils mainly act as effectors rather than initiators of allergic reactions. ► IgE-mediated chronic allergic inflammation of murine skin is basophil-dependent. ► Novel basophil-deficient mouse strains help to define the role of basophils in vivo.

Introduction

Basophils are the least abundant type of granulocytes after neutrophils and eosinophils. They mature in the bone marrow and have a lifespan of about 60 h under steady-state conditions in mice [1]. Basophils are morphologically and functionally very similar to tissue-resident mast cells. Both cell types contain granules that can be stained with basophilic aniline dyes. They both express the αβγ2 form of the high-affinity receptor for IgE (FcɛRI). Interestingly, FcɛRI can also be expressed as signaling competent αγ2 form by subsets of dendritic cells [2, 3••, 4], monocytes [5] and eosinophils [6]. Effector molecules produced by mast cells and basophils include vasodilators like histamine and platelet-activating factor (PAF), leukotriene C4 and the Th2-associated cytokines IL-4 and IL-13 [7]. However, basophils represent a distinct cell lineage and are not a population of immature circulating mast cells.

Section snippets

The early type 2 immune response – are basophils crucial for Th2 polarization?

In analogy to Th1 polarization where early secretion of IL-12 by DCs initiates the Th1 differentiation program it was proposed that an innate source of IL-4 is required for Th2 polarization. Several reports pointed toward an important role for basophils as inducers of Th2 polarization. Mice deficient for interferon response factor 2 (IRF2) or the tyrosine kinase Lyn show increased levels of circulating basophils and a spontaneously Th2-biased phenotype [8, 9]. Furthermore, basophils are

Basophil mobilization and activation by cytokines

Basophils respond to different cytokines that modulate their survival, effector functions and tissue recruitment. IL-3 from T cells is important for basophilia during helminth infection, although IL-3 is not essential for basophil development under steady-state conditions [19, 20]. Basophils also express IL-3 and may thereby regulate their survival in an autocrine manner [21]. In addition, IL-3 exerts an important co-stimulatory function for mediator release. IL-3, IL-18 or IL-33 are potent

Basophils in allergic skin reactions

The recruitment of basophils during allergic skin reactions has been observed in early studies with guinea pigs that developed a ‘cutaneous basophil hypersensitivity’ reaction upon injection of protein antigen with incomplete Freund's adjuvant [27]. Basophils were also identified in human skin of allergic contact dermatitis patients [28] and in allergen-induced patch test sites of atopic dermatitis patients [29]. Basophils are found in skin biopsies and blister fluid of cutaneous late-phase

Basophils in asthma and allergic rhinitis

Basophils were found in large numbers in post-mortem biopsies of fatal asthma [42, 43]. Accumulation of basophils was also observed in bronchial biopsies of atopic asthma patients [44] and nasal washes of allergic rhinitis patients [45]. Basophils probably contribute to pathology since they are the main source of histamine during the late phase response (LPR) after nasal challenge of seasonal allergic rhinitis patients [46]. However, a short-term allergic inflammation model of the murine lung

Basophils and anaphylaxis

Anaphylaxis is a severe systemic allergic response characterized by rapid drop of blood pressure, shortness of breath, reduced body temperature and loss of consciousness. The classical form of anaphylaxis is mediated by histamine released from mast cells that are activated by allergens via crosslinking of surface-bound IgE molecules. Basophils were reported to be responsible for an alternative form of anaphylaxis that is mediated by platelet activating factor (PAF) released from basophils after

Conclusion

Basophil in vivo functions were ignored for a long time owing to their low frequency and lack of specific markers. The observation that basophils can be depleted with antibodies that bind to activating receptors on basophils and mast cells enabled researchers to address the role of basophils in mouse models. Some of these studies proposed that basophils act early during type 2 immune responses as crucial antigen-presenting cells for polarization of Th2 cells. More recent studies with different

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • •• of outstanding interest

Acknowledgements

This work was supported by an ERC starting grant (PAS 241506) from the European Union and by an Emmy Noether grant (Vo944/2-2) from the Deutsche Forschungsgemeinschaft.

References (52)

  • H. Hammad et al.

    Inflammatory dendritic cells – not basophils – are necessary and sufficient for induction of Th2 immunity to inhaled house dust mite allergen

    J Exp Med

    (2010)
  • M.H. Grayson et al.

    Induction of high-affinity IgE receptor on lung dendritic cells during viral infection leads to mucous cell metaplasia

    J Exp Med

    (2007)
  • D. Maurer et al.

    Expression of functional high affinity immunoglobulin E receptors (Fc epsilon RI) on monocytes of atopic individuals

    J Exp Med

    (1994)
  • A.S. Gounni et al.

    High-affinity IgE receptor on eosinophils is involved in defence against parasites

    Nature

    (1994)
  • E. Schneider et al.

    Basophils: new players in the cytokine network

    Eur Cytokine Netw

    (2010)
  • S. Hida et al.

    Negative control of basophil expansion by IRF-2 critical for the regulation of Th1/Th2 balance

    Blood

    (2005)
  • S. Kim et al.

    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)
  • J.G. Perrigoue et al.

    MHC class II-dependent basophil-CD4+ T cell interactions promote T(H)2 cytokine-dependent immunity

    Nat Immunol

    (2009)
  • H. Tang et al.

    The T helper type 2 response to cysteine proteases requires dendritic cell-basophil cooperation via ROS-mediated signaling

    Nat Immunol

    (2010)
  • C.L. Sokol et al.

    Basophils function as antigen-presenting cells for an allergen-induced T helper type 2 response

    Nat Immunol

    (2009)
  • T. Yoshimoto et al.

    Basophils contribute to T(H)2-IgE responses in vivo via IL-4 production and presentation of peptide-MHC class II complexes to CD4+ T cells

    Nat Immunol

    (2009)
  • B.M. Sullivan et al.

    Genetic analysis of basophil function in vivo

    Nat Immunol

    (2011)
  • A.T. Phythian-Adams et al.

    CD11c depletion severely disrupts Th2 induction and development in vivo

    J Exp Med

    (2010)
  • T. Shen et al.

    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)
  • C.S. Lantz et al.

    Role for interleukin-3 in mast-cell and basophil development and in immunity to parasites

    Nature

    (1998)
  • J.T. Schroeder et al.

    Human basophils secrete IL-3: evidence of autocrine priming for phenotypic and functional responses in allergic disease

    J Immunol

    (2009)
  • Cited by (31)

    • Innate immunity as the orchestrator of allergic airway inflammation and resolution in asthma

      2017, International Immunopharmacology
      Citation Excerpt :

      Their relative small numbers and their resemblance to MCs have taken basophils out of the spotlight for some time, therefore our knowledge on their role in the initiation and establishment of allergic responses is rather limited. However, recent work with novel mouse models has provided evidence that basophils exert essential effector functions in Th2-mediated allergic responses [129,130]. Basophils arise from a granulocyte precursor in the bone marrow which is common for eosinophils and MCs; however, unlike the latter, basophils exit to the periphery with a fully mature phenotype [131].

    • Mucosal Eosinophils

      2015, Mucosal Immunology: Fourth Edition
    • Mouse Models of Allergic Airways Disease

      2014, Middleton's Allergy: Principles and Practice: Eighth Edition
    • Pathophysiology of Allergic Inflammation

      2014, Middleton's Allergy: Principles and Practice: Eighth Edition
    View all citing articles on Scopus
    View full text