The importance of the interaction between IgG and Fc receptors has been demonstrated in experimental models, whereby there is a diminished macrophage effector function induced after IgG1-mediated phagocytosis in Fc chain knock-out mice [18]. is associated with protection against schistosome infection. This relationship indicates a mechanistic link between the innate and adaptive immune responses to helminth infection in protection against infection. Further understanding the elements of a protective immune response in schistosomiasis may aid in efforts to develop a protective vaccine against this disease. Author Summary Schistosomiasis is a parasitic disease caused by the parasite spp. Over 240 million people are infected worldwide, mainly in Sub-Saharan Africa, but an efficacious, protective OICR-0547 vaccine has yet to be found. Protection against schistosome infection in individuals living in endemic areas is mediated by antibodies. In particular, IgG1 antibody has been shown to be protective against infection in individuals living in endemic areas, and eliciting IgG1 production has become a cornerstone of vaccine development efforts. However, little is known about the mechanisms by which IgG1 induces protection. The cell surface molecule CD16 is an IgG antibody receptor expressed on monocytes and binds preferentially to IgG antibody subclasses. The work presented here thus investigates the relationship between IgG levels and the monocyte CD16 receptor in a population endemically exposed to infection with schistosomes. We present results linking CD16 expression with IgG1 levels, whereby uninfected individuals have a positive relationship between IgG1 and CD16 expression levels, while schistosome infected individuals did not show any statistically significant relationship between the two. Thus we provide evidence to suggest a mechanistic link between the innate and adaptive immune response in parasitic infection, associating monocyte CD16 expression with a protective immune response. Introduction An estimated 200 million people worldwide are infected with helminths of the genus Sand are endemic, causing significant morbidity amongst affected communities [1]. Infection and disease are controlled by treatment with the drug praziquantel (PZQ), and the World Health Organization (WHO) recommends protective chemotherapy via mass drug administration (MDA) with PZQ in endemic areas [2]. There is mounting pressure to develop a vaccine against schistosomiasis, which would provide long term protection to the 650 million people at risk of exposure [3], and pre-empt the development of drug resistance. Current vaccine development research focuses on determining which naturally developed immune responses are associated with protective immunity that develops in the context of endemic exposure to infection, and investigate ways of inducing those responses artificially whilst OICR-0547 avoiding a pathological response [4], [5]. While significant progress has been made in characterising humoral and cellular responses in experimental models, relatively less work has been conducted relating the innate and adaptive arms of the immune system in schistosome infected versus uninfected humans. In particular, there is a paucity of studies simultaneously determining cellular and related humoral responses associated with natural protection against schistosome infection. Mouse monoclonal to CMyc Tag.c Myc tag antibody is part of the Tag series of antibodies, the best quality in the research. The immunogen of c Myc tag antibody is a synthetic peptide corresponding to residues 410 419 of the human p62 c myc protein conjugated to KLH. C Myc tag antibody is suitable for detecting the expression level of c Myc or its fusion proteins where the c Myc tag is terminal or internal Experimental studies have shown links between innate cells from the myeloid lineage and resistance to helminth infection. For example, murine macrophages and are involved with tissue repair and fibrosis [6], [7], as well as in limiting pathology by regulating Type 2 cytokine production [8], [9] and inhibiting T cell proliferation [10]. This current study focused on circulating monocytes, myeloid cells related developmentally to macrophages, which are present in the blood vessels and are thus easily accessible for investigation in humans. Studies from several decades ago showed a direct role ex vivo for human PBMC-derived monocytes in the killing of schistosomula [11]C[13]. Similar to macrophages, monocytes display phagocytic capabilities and express varying levels of the FcRIIIa (also known as the CD16 receptor) [14], which is related to distinctions in their phenotype and function in a range of pro-inflammatory conditions [15], [16]. The Fc receptors have a critical role in immune regulation, acting as a link between the humoral and innate cellular arms of the immune response [17]. In humans, the CD16 receptor exhibits high affinity binding to the Fc portion of IgG antibodies, with high affinity binding demonstrated to IgG1 and IgG3, which leads to phagocytosis, release of inflammatory mediators and clearance of immune complexes [14]. The importance of the interaction between IgG and Fc receptors has been demonstrated in experimental models, whereby there is a diminished macrophage effector function induced after IgG1-mediated phagocytosis in Fc chain knock-out mice [18]. OICR-0547 Furthermore, infection exacerbated granuloma formation and fibrosis in both Fc receptor and in B cell deficient mice [19], highlighting the importance of antibody signalling. OICR-0547