Eosinophils from Physiology to Disease: A Comprehensive Review

Figure 2

Eosinophil interactions with cells and tissues. Eosinophils are part of a complex network of signalling molecules and exert a wide range of behaviours towards interacting cells and tissues. Bidirectional cytokine signalling favours the reciprocal activation of group 2 innate lymphoid cells (ILC-2) and eosinophils, Th2 cells, and eosinophils as well as mast cells and eosinophils. ILC-2 are a major source of IL5 for eosinophils, which in turn can maintain ILC-2 activation through the release of IL4. ILC-2 play also a pivotal role in the cross-talk between tissues and inflammatory cells, as they respond rapidly to tissue-derived IL25, IL33, and thymic stromal lymphopoietin (TSLP) and promote Th2-responses by secreting IL4. Th2 cells favour eosinophil activation and survival by releasing an array of moieties, primarily IL5. Eosinophils in turn are able to sustain Th2 responses through the production of IL25. Downstream Th2 cells, eosinophils contribute to the humoral adaptive response by releasing plasma cell survival factors such as IL6 or A proliferation inducing ligand (APRIL) and by recognising class G and class E immunoglobulin through their surface receptors. Mast cells respond to the release of eosinophil-derived MBP and are major triggers of acute inflammation under several inflammatory conditions. In addition, they promote eosinophil activation by releasing prostaglandins such as prostaglandin D2 (PGD2), chemokines such as CCL5, and leukotrienes. Leukotrienes are well-known mediators of acute and chronic airways inflammation. Thus, not surprisingly, aspirin exposure and eventual enhanced leukotriene production can cause respiratory hyperresponsiveness in association with eosinophilia. Mast cells also secrete chymase, which promotes eosinophil survival by dampening apoptosis cell programmes. Eosinophils themselves are able to extend their lifespan by releasing IL5 and CCL5 in auto/paracrine manner. Inflamed tissues propitiate eosinophil recruitment by releasing chemoattractant such as CCL5, CCL11, CCL24, and CCL26. TSLP has a major role in eosinophil recruitment into the respiratory tract. Eosinophils in turn jeopardize tissue integrity by disrupting the architecture of the extracellular matrix and by causing direct cellular damage through the release of specific granules content. Eosinophils are also able to interact with intravascular effectors of innate immunity such as platelets. Eosinophils contribute to platelet activation by releasing platelet activating factor (PAF) as well as MBP and EPO, while platelets affect eosinophil activation through the production of CCL5, CCL17, CXCL4, and IL1β and the engagement of P-selectin and CD40 with PSGL1 and CD40ligand, respectively. The reciprocal interactions between platelets and eosinophils favour the development of tissue inflammation and remodelling (especially at the level of the respiratory tract) and are possibly involved in the development of thrombosis. Activated eosinophils express tissue factor (TF) and are themselves able to promote thrombin generation. Under inflammatory conditions, eosinophils can also form extracellular traps of mitochondrial decondensed DNA, possibly contributing to the induction and maintenance of chronic inflammation.