Welcome to the neighborhood: epithelial cell-derived cytokines license innate and adaptive immune responses at mucosal sites. strike a delicate balance between attempts to neutralize the infectious assault versus limitation of damage to host tissues. Among the most important cell types during helminthic invasion are granulocytes: eosinophils, neutrophils and basophils. Depending on the specific context, these leukocytes may have pivotal roles in host protection, immunopathology, or facilitation of helminth establishment. This review provides an overview of the function of granulocytes in helminthic infections. protein synthesis; a particularly important characteristic that highlights their key role in innate and adaptive immune functions. The capability of granulocytes, most notably eosinophils, to release toxic cationic proteins has been considered historically as an effector mechanism against extracellular organisms [4], although these molecules have also been implicated in tissue damage. Thus, granulocyte-mediated immunopathology is observed in hyperre-activity during some nematode infections and is also frequently manifested in allergic responses such as asthma [5]. The release of granule proteins can be induced through binding MRS 2578 of antigen-IgE complexes to the high affinity IgE receptor (FcRI) that triggers a tightly controlled phosphorylation cascade [6]. The classical view of granulocyte function has been reconsidered over the last decades, MRS 2578 as new data have demonstrated that this cell type has roles other than that of a terminal effector cell [5, 7]. The functional analysis of granulocytes in helminth infections relies on interventional studies KIT and includes suitable animal models in conjunction with immunological or genetic tools to interfere with normal granulocyte development and function. Despite the caveat that laboratory model organisms may not always be the natural host of the parasite, and therefore cannot MRS 2578 represent all processes observed in natural infections of livestock or humans, clearly many paradigms translate well between the species and have led not only to greater understanding of parasitic diseases, but in several cases, to successful therapies. This review is not intended to cover the entire field of granulocyte biology but to focus on their functions in relation to a particularly complex foe, the helminth parasites. In particular the role of eosinophils, basophils and neutrophils in host protection, immunopathology or facilitation of helminth establishment will be discussed. TH2 IMMUNITY TO HELMINTH INFECTIONS In response to an infection, a variety of cells becomes activated and collaborates in the effort to control and eliminate invading pathogens (see Fig. ?11). TH1 cells mainly produce IFN, which is important for classical macrophage activation and the clearance of many intracellular microbes. Large extracellular pathogens face immune mechanisms that are of a TH2-type, characterized by an elevation of peripheral blood eosinophilia and accompanied by profound increases in cytokine production Interleukin (IL)-3, IL-4, IL-5, IL-9, IL-13) and granulocyte macrophage colony-stimulating factor (GM-CSF) as well as induction of the antibody isotypes immunoglobulin (Ig) G1, IgG4 and IgE. In mice lacking the key component of TH2-type immunity, CD4+ T cells, protective immunity to the nematodes [9] and other helminths [10] is lost, providing evidence to support the importance of such responses in parasite clearance. Historically, it was hypothesized that TH2 responses are induced by suboptimal antigen presentation and consequently, ineffective stimulation of the TH1 pathway. However, helminth products can drive TH2 immunity even in the presence of TH1 inducers. For example, when stimulated with soluble egg antigen (SEA), DC are able to induce TH2 responses in the presence of bacterial TH1 stimuli [11]. Open in a separate window Fig. (1). T cell mediated effector mechanisms against pathogens. Innate immune mechanisms are the first to respond to place against infection. They consist of soluble factors, such as complement proteins, together with many cellular components including mast cells, macrophages, dendritic cells, natural killer cells and granulocytes (eosinophils, neutrophils and basophils). Adaptive immune responses develop more slowly, but result in increased antigen specificity and immunological memory, and are orchestrated by CD8+ T MRS 2578 cells, CD4+ T cells and B lymphocytes. Among the.