Effector functions of eosinophils in schistosomiasis

The dual function of eosinophils is clearly illustred in schistosomiasis. Well equipped in membrane receptors for immunoglobulins and complement, and due to the presence of granule basic proteins, eosinophils can become cytotoxic for parasite larvae and thus participate to protective immunity. However mediators can also exert their cytolytic effect on normal cells or tissues, inducing therefore pathology. Through ADCC mechanisms against schistosome larvae in vitro involving different antibody isotypes (IgG, IgE and IgA) and also in experiments performed in vivo, eosinophils have been clearly involved in protective immunity. Although no direct evidence of the protective role of eosinophils were brought in humans, the striking association of eosinophil-dependent cytotoxic antibody isotypes with resistance to reinfection (for instance IgE and IgA antibodies), whereas in vitro blocking antibody isotypes (IgG4, IgM) were detected in susceptible subjects, strongly, suggested the participation of eosinophils in antibody-dependent protective immune response. However eosinophils could also participate to granuloma formation around S. mansoni eggs and consequently to the pathological reactions induced by schistosomiasis

Role of the High Affinity Immunoglobulin E Receptor in Bacterial Translocation and Intestinal Inflammation

A role for immunoglobulin E and its high affinity receptor (FcεRI) in the control of bacterial pathogenicity and intestinal inflammation has been suggested, but relevant animal models are lacking. Here we compare transgenic mice expressing a humanized FcεRI (hFcεRI), with a cell distribution similar to that in humans, to FcεRI-deficient animals. In hFcεRI transgenic mice, levels of colonic interleukin 4 were higher, the composition of fecal flora was greatly modified, and bacterial translocation towards mesenteric lymph nodes was increased. In hFcεRI transgenic mice, 2,4,6-tri-nitrobenzenesulfonic acid (TNBS)-induced colitis was also more pronounced, whereas FcεRI-deficient animals were protected from colitis, demonstrating that FcεRI can affect the onset of intestinal inflammation

Peroxisome Proliferator–activated Receptors α and γ Down-regulate Allergic Inflammation and Eosinophil Activation

Allergic asthma is characterized by airway hyperresponsiveness, eosinophilia, and mucus accumulation and is associated with increased IgE concentrations. We demonstrate here that peroxisome proliferator–activated receptors (PPARs), PPAR-α and PPAR-γ, which have been shown recently to be involved in the regulation of various cell types within the immune system, decrease antigen-induced airway hyperresponsiveness, lung inflammation, eosinophilia, cytokine production, and GATA-3 expression as well as serum levels of antigen-specific IgE in a murine model of human asthma. In addition, we demonstrate that PPAR-α and -γ are expressed in eosinophils and their activation inhibits in vitro chemotaxis and antibody-dependent cellular cytotoxicity. Thus, PPAR-α and -γ (co)agonists might be of therapeutic interest for the regulation of allergic or inflammatory reactions by targeting both regulatory and effector cells involved in the immune response

A Functional γδTCR/CD3 Complex Distinct from γδT Cells Is Expressed by Human Eosinophils

BACKGROUND:Eosinophils are effector cells during parasitic infections and allergic responses. However, their contribution to innate immunity has been only recently unravelled. METHODOLOGY/PRINCIPAL FINDINGS:Here we show that human eosinophils express CD3 and gammadelta T Cell Receptor (TCR) but not alphabeta TCR. Surface expression of gammadeltaTCR/CD3 is heterogeneous between eosinophil donors and inducible by mycobacterial ligands. Surface immunoprecipitation revealed expression of the full gammadeltaTCR/CD3 complex. Real-time PCR amplification for CD3, gamma and delta TCR constant regions transcripts showed a significantly lower expression in eosinophils than in gammadeltaT cells. Limited TCR rearrangements occur in eosinophils as shown by spectratyping analysis of CDR3 length profiles and in situ hybridization. Release by eosinophils of Reactive Oxygen Species, granule proteins, Eosinophil Peroxidase and Eosinophil-Derived Neurotoxin and cytokines (IFN-gamma and TNF-alpha) was observed following activation by gammadeltaTCR-specific agonists or by mycobacteria. These effects were inhibited by anti-gammadeltaTCR blocking antibodies and antagonists. Moreover, gammadeltaTCR/CD3 was involved in eosinophil cytotoxicity against tumor cells. CONCLUSIONS/SIGNIFICANCE:Our results provide evidence that human eosinophils express a functional gammadeltaTCR/CD3 with similar, but not identical, characteristics to gammadeltaTCR from gammadeltaT cells. We propose that this receptor contributes to eosinophil innate responses against mycobacteria and tumors and may represent an additional link between lymphoid and myeloid lineages

The presence of four iron-containing superoxide dismutase isozymes in Trypanosomatidae : characterization, subcellular localization, and phylogenetic origin in Trypanosoma brucei

Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Elsevier B. V. for personal use, not for redistribution. The definitive version was published in Free Radical Biology and Medicine 40 (2006): 210-225, doi:10.1016/j.freeradbiomed.2005.06.021.Metalloenzymes such as the superoxide dismutases (SODs) form part of a defense mechanism that helps protect obligate and facultative aerobic organisms from oxygen toxicity and damage. Here, we report the presence in the trypanosomatid genomes of four SOD genes: soda, sodb1 and sodb2 and a newly identified sodc. All four genes of Trypanosoma brucei have been cloned (Tbsods), sequenced and overexpressed in Escherichia coli and shown to encode active dimeric FeSOD isozymes. Homology modelling of the structures of all four enzymes using available X-ray crystal structures of homologs showed that the four TbSOD structures were nearly identical. Subcellular localization using GFP-fusion proteins in procyclic insect trypomastigotes shows that TbSODB1 is mainly cytosolic, with a minor glycosomal component, TbSODB2 is mainly glycosomal with some activity in the cytosol and TbSODA and TbSODC are both mitochondrial isozymes. Phylogenetic studies of all available trypanosomatid SODs and 106 dimeric FeSODs and closely related cambialistic dimeric SOD sequences suggest that the trypanosomatid SODs have all been acquired by more than one event of horizontal gene transfer, followed by events of gene duplication.This work was supported by Interuniversity Attraction Pole programme of the Belgian Government P5/29 (to F.R.O.), the Institut National de la Santé et de la Recherche Médicale, the Institut Pasteur de Lille, and the Centre National de la Recherche Scientifique (to E.V.). F.D. was supported by a grant from the Ministère Français de l’Education Nationale, de la Recherche et de la Technologie. D.G. was supported by an ICP postdoctoral fellowship