Recently our group described that Nattectin, a C-type lectin of the venom of Thalassophryne nattereri shows a potent pro-inflammatory capacity. Here, we demonstrated that Nattectin is able to induce M1 macrophage marker iNOS, and up-regulate the expression of MHC class II, CD80, CD86 and CD40 molecules. The increase in MHC class II and CD49a integrin expression with MMP-9 production and endocytic capacity depend on lectin function of Nattectin. Moreover, the polarization of peritoneal and bone marrow-derived macrophages induced by Nattectin to M1 profile is dependent on Th1 cytokines (IL-12 and IFN-γ), and negatively regulated by Th2 cytokines (IL-4, IL-10 and IL-13). Also we reveal that IL-4 play a dual role in this polarization: a regular action of IL-4 was seen in the negative regulation of the CD40 expression, but an unexpected positive regulation was seen in the expression of CCR7 and MHC class II. Finally, our in vivo studies showed that the influx of neutrophils and small peritoneal macrophage--F4/80(low)MHCII(hi) induced by Nattectin is totally dependent on IL-4 and IFN-γ cytokines. Furthermore, the induction of IL-6 release is negatively regulated by IL-4 and positively regulated by IL-12 and IFN-γ. Together, the results allowed us to expand the knowledge about the regulation of macrophage activation, as well as confirmed the ability of Nattectin, a fish C-type lectin, as an important immunomodulatory agent.

We hypothesized that beyond the Thalassophryne nattereri venoms ability to induce in mice a strong specific-Th2 response with high levels of specific IgE/IgG1, it would be able to trigger anaphylaxis in sensitized individuals. To investigate whether the venom is capable of inducing an allergic reaction in mice and characterize soluble and cellular mediators involved in this process, BALB/c female mice were sensitized intraperitoneally with decreasing-dose of venom at weekly intervals for 4 weeks and challenged by intraperitoneal, oral or epicutaneous routes with venom 2 weeks later. Our data show that sensitized-mice challenged by all routes showed intense symptoms of anaphylaxis, dependent on the anaphylactic IgG1 and IgE antibodies and mast cells. The late-phase reaction developed after initial symptoms was characterized by the influx of eosinophils, dependent on IL-5, IL-17A and eotaxin produced by Th2 cells in inflamed lungs and skin draining lymph-nodes. Using C57BL/6 deficient mice we demonstrated that IL-4 KO mice failed to develop anaphylactic symptoms or local Th2 inflammation, producing low levels of IgG1 and increased levels of IgG2a. Together our results demonstrated that the venom of T. nattereri has allergenic proteins that can trigger an allergic process, a phenomenon IgE-IgG1 dependent, IL-4-mediated and negatively regulated by IFN-γ.

LOCID). The aim of the study was to assess the severity of CVID using the ''AS'', which focuses mainly on cumulative damage to organs such as result of infections, autoimmunity or inflammation. METHODS: We retrospectively study charts of patients with CVID, seen at a Reference Center, and applied the "AS". The score is based on the severity of the complications of each organ, classified as mild 5 1point (without long-term morbidity), moderate 5 5points (short and long-term morbidity) and severe 5 10points (fatal or with the potential to severe disability). RESULTS: We evaluated 29 charts (69% male), with a median of age 36.3 y. The lung was the most affected organ, with manifestations in 69%, mainly bronchiectasis (58.6%). Gastrointestinal complications such as severe enteritis were the second most frequent (20.7%). Autoimmune manifestations were present in 41.4%, mainly cytopenias. Three patients had some type of malignancy. The total score in the analyzed population ranged from 0 to 47. Patients with a score above 35 had CD4 lymphopenia during evolution in 75% of cases. CONCLUSIONS: The "AS'' can be a useful tool for the identification of patients with LOCID, in addition to providing a linear assessment of the evolution of each patient, as well as a strategy until the genetic clarification to differentiate the CVID from the monogenic CIVD-like.

Esta dissertação está de acordo com as seguintes normas, em vigor no momento desta publicação: Referências: adaptado de International Committee of Medical Journals Editors (Vancouver).