The contribution that the subset of leukocytes known as basophils makes to immunity is controversial. A clear picture of the function of basophils has been slow to emerge, mainly due to functional studies on basophils in vivo being hampered by limitations in reagent availability and specificity. These issues were discussed by Schwartz and Voehringer in the June 2011 issue of BioEssays 1. The authors speculated that many outstanding issues surrounding basophil function would soon be resolved following recent development of specific means to delete and track basophils in vivo. Indeed, in subsequent months more definitive determination of basophil function has emerged using these tools. Thus, we here provide a brief update on the function of basophils in immunity. Whether basophils serve as antigen-presenting cells (APCs) that prime TH2 cell responses, the T cell subset controlling allergic and anti-parasitic immunity, was controversial 1. Sullivan and colleagues demonstrated that basophils do not play an essential role in the priming of TH2 cells following Schistosoma mansoni egg infection or in the papain-induced model of allergy 2. Moreover, their data revealed that basophils do not form stable conjugates with antigen-specific T cells, a prerequisite for an effective APC. The same study addressed another controversy pertaining to the function of basophils as effector cells in host defense against parasites. It was demonstrated that basophils provide a non-redundant source of IL-4 in infected tissues, which, in collaboration with T cell-derived IL-4, mediated worm expulsion following Nippostrongylus brasiliensis infection 2. Thus, a picture is now emerging whereby anti-parasitic immunity is not reliant on basophils as APCs, but requires cooperative responses between basophils and CD4+ T cells as effector cells. One explanation for discrepancies regarding reported functions of basophils may also be explained by recent findings demonstrating significant heterogeneity in basophils. Whilst IL-3 has long been considered the critical factor mediating basophil differentiation, recent studies have identified a novel function for the cytokine thymic stromal lymphopoetin (TSLP), which drives production of basophils distinct from those reliant on IL-3 3, 4. These studies further demonstrated that peripheral basophillia in murine models of atopic dermatitis and Trichinella spiralis infection are TSLP-dependent and can occur in the presence or absence of IL-3, raising the question of whether specific subtypes of basophils mediate distinct responses. Basophils have also been implicated as important effector cells driving pathogenesis of IgE-mediated chronic allergic inflammation (IgE-CAI) of the skin. However, recent work using new genetic tools to delete basophils surprisingly identified an anti-inflammatory role of basophils in this setting. Egawa et al. 5 demonstrated that basophils promoted differentiation of inflammatory monocytes into anti-inflammatory M2 macrophages rather than typical inflammatory M1 macrophages. Basophil-induced M2 macrophage differentiation subsequently dampened allergic inflammation during IgE-CAI. Thus, an intriguing possibility now emerges that basophils function as important regulators of macrophage differentiation in a range of inflammatory settings, which could have important implications for treatment in various inflammatory pathologies. Thus, as the important questions regarding the function of basophils in mice begin to be definitively addressed with novel genetic tools, new questions arise. Are there subsets of basophils yet to be identified that are capable of acting as APCs? Does boosting basophil responses provide a means to control macrophage-driven inflammation? Finally, and crucially, do these findings with regard to basophils in murine experimental models accurately reflect the functional significance of basophils in humans?
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Open Access
Aug 1, 2014
Nikhil Dhingra + 1
