Nonredundant Roles of Basophils in Immunity

Abstract

Basophils are the rarest granulocytes and represent less than 1% of peripheral blood leukocytes. They are evolutionarily conserved in many animal species, but their functional significance remained an enigma long after their discovery by Paul Ehrlich in 1879. Studies of basophils were hindered by their rarity, by difficulties in identifying them, and by the paucity of useful analytical tools. Because basophils display several characteristics shared by tissue-resident mast cells, they were often considered minor and possibly redundant relatives of mast cells or even blood-circulating precursors of mast cells. However, newly developed tools for their functional analysis, including basophil-depleting antibodies and genetically engineered mice deficient only in basophils, have fueled basophil research and defined previously unrecognized functions of basophils. We now appreciate that basophils play nonredundant roles in acquired immunity regulation, protective immunity to pathogens, and immunological disorders such as allergy and autoimmunity.

GATA-1 regulates the generation and function of basophils

“…We illustrated in the present study that ΔdblGATA mice showed impaired acquired protection against hilminth infection due to basophil anomaly. Considering recent advances in our understanding of functional significance of basophils in various immune responses (22)(23)(24)(25)(26)(27)(28), this finding raises concern about the possibility that certain functions of basophils might have been erroneously interpreted as those of eosinophils in studies using ΔdblGATA mice as eosinophil-deficient mice. Two distinct eosinophil-deficient mouse strains, ΔdblGATA and PHIL, were analyzed to clarify the role of eosinophils in pathogenesis of asthma, resulting in some conflicting results (42,43).…”

“…Accordingly, basophils have often erroneously been considered as minor and redundant relatives of mast cells or blood-circulating precursors of tissue-resident mast cells, and have long been neglected in immunological studies (21). However, recent development of analytical tools for basophil function in vivo, including basophil-deficient mice, has identified pivotal and nonredundant roles for basophils in a variety of immune responses, such as allergic reactions, protective immunity against parasitic infections, and regulation of innate and acquired immunity (22)(23)(24)(25)(26)(27)(28). Nevertheless, the origin and developmental pathway of basophils, including transcription factors regulating their differentiation, still remain ill-defined compared with those of other hematopoietic cells.…”

Signaling pathways activated by a protease allergen in basophils

“…Basophils play multiple roles in type 2 immunity and allergy (11)(12)(13). Basophils also have been shown to be activated by various cysteine proteases, including papain, bromelain (9), and Der p 1, an allergen produced by the house dust mite Dermatophagoides pteronyssinus (14).…”

Basophil-associated OX40 Ligand Participates in the Initiation of Th2 Responses during Airway Inflammation

“…Numerous studies have demonstrated that basophils not only play crucial roles in the effector phase, but also critically participate in the initiation of Th2-centered immune responses (7)(8)(9)(10)(11). Using an ovalbumin (OVA)-induced allergic airway inflammation mouse model, we previously showed that basophils acted as a primary inducer of the Th2 immunity, evident by increased OVA-specific immunoglobulin E (OVA-sIgE) and IL-4 levels both in serum and bronchial alveolar lavage fluid (BALF), and increased proportion of Th2 cells in the spleen after transfusion of lung basophils derived from OVA-challenged mice into wild-type (WT) mice (12).…”