Trends in Parasitology
Volume 25, Issue 12, December 2009, Pages 551-556
Journal home page for Trends in Parasitology

Review
The role of basophils in helminth infection

https://doi.org/10.1016/j.pt.2009.09.004Get rights and content

Protective immunity against gastrointestinal and tissue dwelling helminths is coordinated by interaction of different effector cells of the innate and adaptive immune system. Helminths induce a strong type 2 immune response which is characterized by high levels of IgE and increased numbers of Th2 cells, eosinophils, mast cells and basophils. Basophils are rapidly mobilized after helminth infection and can be efficiently recruited into lymphoid and peripheral tissues where they execute their effector functions. Recent work demonstrated that basophils contribute to initiation and execution of type 2 immunity. This review discusses the potential role of basophils for protective immunity against helminths.

Section snippets

Basophils are effector cells for protective type 2 immunity against helminths

Helminths are very successful parasites that currently infect more than two billion people [1]. Infections with helminths tend to be chronic and often result in malnutrition, anemia, growth retardation and increased susceptibility to infection with opportunistic pathogens. In addition, helminth infections cause a major problem for domestic livestock production, worldwide. Most helminth infections can be cured very efficiently by drug treatment; however, individuals can be rapidly reinfected

Identification of basophils by flow cytometry and immune histology

Basophils represent <0.3% of peripheral blood leukocytes and their biological role is not well defined although they were identified as long as 130 years ago by Paul Ehrlich [5]. Research on basophils has been difficult, given the fact that basophils occur at a very low frequency, have a short lifespan and lack specific surface markers. In addition, murine basophils appear to have fewer granules than basophils of other species so that murine basophils (in contrast to their human homologs)

Basophil development, lineage relationship and turnover

Basophil-like cells are present early during ontogeny and can be found at low frequencies in the fetal liver at embryonic day 16.5, where they already express IL-4 and IL-3Rα, but still lack expression of FcɛRI [17]. Basophils are phenotypically and functionally closely related to mast cells and eosinophils. A common precursor for mast cells and basophils has recently been identified in the spleen, whereas a more basophil-restricted precursor was found in the bone marrow [18]. The transcription

Basophils as initiators of a type 2 immune response

Immune responses against helminths cause differentiation of naïve T cells into Th2 cells in draining lymph nodes of infected subjects. IL-4 plays an important role in this process and is especially required to stabilize Th2 cell fate. It has been proposed that IL-4-producing cells of the innate immune system (such as mast cells, eosinophils or basophils) might provide the initial source of IL-4 to drive T cell polarization toward Th2 cells. In fact, it has been shown that mice that lack the

Basophil mobilization and activation by helminths

Rag-deficient mice show an attenuated mobilization of basophils after N. brasiliensis infection [21]. Transfer of CD4 T cells from IL-4 knockout [9] or IL-4/IL-13 double knockout mice [17] could completely restore this defect suggesting that basophil mobilization does not depend on Th2 cells but requires the presence of CD4 T cells, consistent with the observation that T cell-derived IL-3 is required for helminth-induced basophilia [21].

Early activation of basophils by helminths could be caused

Basophils as effector cells against helminths

Basophils produce various cytokines which are important components for orchestration of an efficient type 2 immune response. Stimulation of human or murine basophils with extracts from helminths induces de novo synthesis and release of IL-4, IL-5 and IL-13 17, 55. IL-5 mobilizes eosinophils from the bone marrow and increases viability from 5% to 40% within 24 h of in vitro culture [59]. Indeed, basophil-derived IL-5 seems to play an important role for helminth-induced eosinophilia because

Basophils during secondary infection with helminths

Basophils can rapidly release IL-4 upon secondary challenge with a model antigen and might thereby promote the rapid and enhanced development of Th2 cells which is characteristic of a memory type 2 response [67]. IL-4 released from basophils and/or memory Th2 cells could then lead to enhanced production of IgE and IgG1. Basophils were demonstrated to promote the memory response to Streptococcus pneumoniae because basophil depletion before challenge infection resulted in lower serum IgG1 and

Concluding remarks

Basophils produce large amounts of Th2-associated cytokines such as IL-4, IL-5 and IL-13 which are important mediators for protective immunity against most helminths. A large number of different activating receptors on basophils enables these cells to respond quickly to inflammatory signals that are induced by helminth infections. Basophils derived IL-4/IL-13 can enhance the initiation of primary or secondary type 2 immune responses, although it might not be essential (Figure 1). In addition,

Future challenges

Functional characterization of murine basophils over the past 5 years uncovered many different effector functions of this rare and still enigmatic cell type. However, we are just beginning to understand their role during different stages of an immune response. We still know little about the development of basophils and their lineage relationship with mast cells and eosinophils. The chemotactic factors that recruit basophils into tissues and the cell types with which they interact are not well

References (70)

  • Y. Tsujimura

    Basophils play a pivotal role in immunoglobulin-G-mediated but not immunoglobulin-E-mediated systemic anaphylaxis

    Immunity

    (2008)
  • Y. Zhang

    The chitin synthase genes chs-1 and chs-2 are essential for C. elegans development and responsible for chitin deposition in the eggshell and pharynx, respectively

    Dev. Biol.

    (2005)
  • V. Shpacovitch

    Protease-activated receptors: novel PARtners in innate immunity

    Trends Immunol.

    (2007)
  • B. Dibbert

    Role for Bcl-xL in delayed eosinophil apoptosis mediated by granulocyte-macrophage colony-stimulating factor and interleukin-5

    Blood

    (1998)
  • K. Obata

    Basophils are essential initiators of a novel type of chronic allergic inflammation

    Blood

    (2007)
  • D.R. Herbert

    Alternative macrophage activation is essential for survival during schistosomiasis and downmodulates T helper 1 responses and immunopathology

    Immunity

    (2004)
  • K.D. McCoy

    Polyclonal and specific antibodies mediate protective immunity against enteric helminth infection

    Cell Host Microbe

    (2008)
  • W. Wojciechowski

    Cytokine-producing effector B cells regulate type 2 immunity to H. polygyrus

    Immunity

    (2009)
  • E. Mitre et al.

    IgE memory: persistence of antigen-specific IgE responses years after treatment of human filarial infections

    J. Allergy Clin. Immunol.

    (2006)
  • P.J. Hotez

    Helminth infections: the great neglected tropical diseases

    J. Clin. Invest.

    (2008)
  • M.J. Doenhoff

    Praziquantel: mechanisms of action, resistance and new derivatives for schistosomiasis

    Curr. Opin. Infect. Dis.

    (2008)
  • R.M. Anthony

    Protective immune mechanisms in helminth infection

    Nat. Rev. Immunol.

    (2007)
  • F.D. Finkelman

    Cytokine regulation of host defense against parasitic gastrointestinal nematodes: lessons from studies with rodent models

    Annu. Rev. Immunol.

    (1997)
  • P. Ehrlich

    Beiträge zur Kenntins der granulierten Bindegewebs zellen und der eosinophilen Leukocythen

    Arch. Anat. Physiol. Leipz.

    (1879)
  • C. Urbina

    A new look at basophils in mice

    Int. Arch. Allergy Appl. Immunol.

    (1981)
  • R.A. Seder

    Mouse splenic and bone marrow cell populations that express high-affinity Fc epsilon receptors and produce interleukin 4 are highly enriched in basophils

    Proc. Natl. Acad. Sci. U. S. A.

    (1991)
  • B. Min

    Basophils produce IL-4 and accumulate in tissues after infection with a Th2-inducing parasite

    J. Exp. Med.

    (2004)
  • A. Gessner

    Mast cells, basophils, and eosinophils acquire constitutive IL-4 and IL-13 transcripts during lineage differentiation that are sufficient for rapid cytokine production

    J. Immunol.

    (2005)
  • T. Kojima

    Mast cells and basophils are selectively activated in vitro and in vivo through CD200R3 in an IgE-independent manner

    J. Immunol.

    (2007)
  • T. Koshino

    Identification of basophils by immunohistochemistry in the airways of post-mortem cases of fatal asthma

    Clin. Exp. Allergy

    (1993)
  • A.R. McEuen

    Development and characterization of a monoclonal antibody specific for human basophils and the identification of a unique secretory product of basophil activation

    Lab. Invest.

    (1999)
  • C.L. Kepley

    Identification and partial characterization of a unique marker for human basophils

    J. Immunol.

    (1995)
  • M. Poorafshar

    MMCP-8, the first lineage-specific differentiation marker for mouse basophils. Elevated numbers of potent IL-4-producing and MMCP-8-positive cells in spleens of malaria-infected mice

    Eur. J. Immunol.

    (2000)
  • Y. Arinobu

    Developmental checkpoints of the basophil/mast cell lineages in adult murine hematopoiesis

    Proc. Natl. Acad. Sci. U. S. A.

    (2005)
  • C.S. Lantz

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

    Nature

    (1998)
  • Cited by (55)

    • Innovative vaccine platforms against infectious diseases: Under the scope of the COVID-19 pandemic

      2021, International Journal of Pharmaceutics
      Citation Excerpt :

      Eosinophils and basophils are other granulocytes in the bloodstream but they exist in much lower concentrations, compared with neutrophils. These two types of leucocytes have an important role in hypersensitivity responses and anti-parasite immunity (Falcone et al., 2001; Jiao et al., 2016; Voehringer, 2009). Tissues also have their own immune cells.

    • Hookworm infection: Toward development of safe and effective peptide vaccines

      2021, Journal of Allergy and Clinical Immunology
      Citation Excerpt :

      The effective immune response in mice against adult worms might also be related to mucosal humoral response. However, sufficient data to confirm this assumption, except for the occurrence of STAT-6–dependent TH2 cell responses, are not available98 For example, in roundworm (Heligmosomoides polygyrus) infection in mice, which presents similarly to hookworm infection, IgE did not provide protection against primary infection. In secondary infection, protection was conferred by IgA and IgG, and their levels were correlated with resistance to reinfection.99

    • Artificial white blood cells-WBC substitute

      2021, Nanotechnology for Hematology, Blood Transfusion, and Artificial Blood
    • Gastrointestinal Mucosal Immunology and Mechanisms of Inflammation

      2020, Pediatric Gastrointestinal and Liver Disease, Sixth Edition
    • Alterations in Blood Components

      2018, Comprehensive Toxicology: Third Edition
    View all citing articles on Scopus
    View full text