In this study, we determined that the

excretory–secretory (ES) protein from the parasite Anisakis simplex could elicit neutrophil recruitment and IL-17 production. Interleukin-8 and CXCL1 are known 3-deazaneplanocin A mw to be typical neutrophil attractants in lung inflammation (15,25). In this study, we also determined that the expression of the CXCL1 gene was increased as a result of ES protein treatment. Interleukin-17 is generated and released as a free protein from T-lymphocytes of the memory (CD45RO+) subset (27). Linden suggested that IL-17 can recruit and activate neutrophils in the airways; this recruitment is mediated by the neutrophil chemoattractant IL-8, CXCL1 and macrophage inflammatory protein-2 (27). In this study, the level of IL-17 in the BALF of ES protein and OVA-treated mice was significantly higher than those in the OVA-only treatment group (Figure 1c). In addition, IL-17 producing cells were recruited to the lung and lung draining lymph node as the consequence of intranasal ES protein treatment (Figure 1d,e). The ES proteins were also determined to induce IL-6

that enhances the activation of Th17 cells, and gene expression in lung epithelial cells (Figure 2a). Therefore, Anisakis ES proteins may activate IL-17 producing Navitoclax mouse cells and neutrophil recruitment in the airway via an induction of IL-6 cytokine production in lung epithelial cells. These findings reveal that IL-17 plays a critical role in the Anisakis-associated allergic reaction. Shainheit et al. previously reported that schistosome egg-stimulated dendritic cells plus naive CD4

T cells from Bay 11-7085 CBA mice resulted in increased levels of pre-inflammatory cytokines, as well as IL-17 and the chemokines CXCL1, CXCL2 and CCL2. They demonstrated that after neutralization of IL-23 and IL-1, but not of IL-6 or IL-21, egg-induced IL-17 production was profoundly inhibited. They also emphasized that parasite recognition followed by a genetically determined innate pro-inflammatory response induces the development of Th17 cells, and thus controls the outcome of immunopathology in schistosomiasis (28). Specific recognition of conserved molecular motifs associated with different classes of pathogens – particularly viruses, bacteria, fungi and protozoa – by antigen presenting cells (APCs) can be mediated by pattern recognition receptors (PRRs) including the TLR, C-type lectin and Nod-like receptors (26). Toll-like receptors are important initiators of innate immune responses, owing to their ability to recognize a variety of microbial products harbouring pathogen-associated molecular patterns (PAMPs) (29). However, there are no apparent uniformly expressed PAMPs for helminth parasites, although a number of helminth-derived products have been shown to interact with innate immune cells and to modulate their functions.