Trends in Parasitology
ReviewThe role of basophils in helminth infection
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
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