IPTSP - Instituto de Patologia Tropical e Saúde Pública

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    Análise in silico do papel do receptor imune TREM-1 na infecção pelos Norovírus murino e humano
    (Universidade Federal de Goiás, 2024-01-22) Colmenares, Mike Telemaco Contreras; Sales, Marcelle Figueira Marques da Silva; http://lattes.cnpq.br/0477630359032513; Campos, Helioswilton Sales de; http://lattes.cnpq.br/1386621024118393; Campos, Helioswilton Sales de; Dias, Fátima de Rivero; Silva, Marcos Vinicius da
    In humans, Norovirus (NoV) is one of the main causes of acute diarrheal disease (ADD). Due to the limitations of NoV cultivation, some molecular aspects of its interaction with the host's immune system remain unknown. The triggering receptor expressed on myeloid cells 1 (TREM-1) is associated with the amplification of inflammatory responses and the progression of infections, including viral infections. Thus, we believe that TREM-1 may be involved in the NoV infection. Initially, we investigated the expression of Trem1 and the genes involved in its pathway, in transcriptomic data bank of public domain. In experimental infection with murine Norovirus (MNoV), the expression of Trem1 was increased. We also observed that there is a co-expression of Trem1 and genes involved in the pyroptosis pathway, when compared to those in the apoptosis pathway. The in silico protein-protein interactions were assessed by molecular docking simulations between the Ig-like domain of murine TREM-1 and the P domain of the MNoV VP1 protein. The murine TREM-1 recognized the conserved C´-D´ antigen that is present in the murine VP1. In this regard, and based on phylogenetic criteria, different structures of the VP1 protein of NoV GII.4 strains from different years (1987, 2010, 2012, 2014, 2016 and 2019) were modeled. We performed docking and molecular dynamics (MD) simulations to determine the in silico interaction between the VP1 protein of NoV GII.4 and the Iglike domain of human TREM-1. The DM simulations suggest that there is a basic interaction between human TREM-1 and the NoV VP1 protein, regardless of the year of isolation. Interestingly, we observed changes in the participation of the different complementarity determining regions (CDRs) of TREM-1 when interacting with the domains of the VP1 protein, highlighting the participation of CDR3. Our data strongly suggests the involvement of TREM-1 in the recognition of NoV and its participation in the physiopathology of ADD caused by NoV.
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    Avaliação da resposta imune após vacinação para covid-19
    (Universidade Federal de Goiás, 2023-08-28) Masson, Letícia Carrijo; Fonseca, Simone Gonçalves da; http://lattes.cnpq.br/3823367099967701; http://lattes.cnpq.br/3823367099967701; Fonseca, Simone Gonçalves da; Kipnis, Ana Paula Junqueira; Oliveira, Milton Adriano Pelli de
    Immune responses after COVID-19 vaccination should be evaluated in different populations around the world. This study compared antibody responses induced by ChAdOx1 nCoV-19, CoronaVac, and BNT162b2 vaccines. Blood samples from vaccinees were collected pre- and post-vaccinations with the second and third doses. The study enrolled 78 vaccinees, of whom 62.8% were women, with the following median ages: 26 years—ChAdOx1 nCoV-19; 40 years—CoronaVac; 30 years—BNT162b2. Serum samples were quantified for anti-Receptor Binding Domain (RBD) IgG and anti-RBD IgA and anti-spike IgG by ELISA. After two vaccine doses, BNT162b2 vaccinees produced higher levels of anti-RBD IgA and IgG, and anti-spike IgG compared to ChAdOx1 nCoV-19 and CoronaVac vaccinees. The third dose booster with BNT162b2 induced higher levels of anti-RBD IgA and IgG, and anti-spike IgG in CoronaVac vaccinees. Individuals who reported a SARS-CoV-2 infection before or during the study had higher anti-RBD IgA and IgG production. In conclusion, two doses of the studied vaccines induced detectable levels of anti-RBD IgA and IgG and anti-spike IgG in vaccinees. The heterologous booster with BNT162b2 increased anti-RBD IgA and IgG and anti-spike IgG levels in CoronaVac vaccinees and anti-RBD IgA levels in ChAdOx1 nCoV-19 vaccinees. Furthermore, SARS-CoV-2 infection induced higher anti-RBD IgA and IgG levels in CoronaVac vaccinees. Novembro
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    Análise da proliferação de amastigotas de Leishmania (Viannia) braziliensis em macrófagos murinos
    (Universidade Federal de Goiás, 2021-09-30) Teixeira, Mirian Vieira; Oliveira, Milton Adriano Pelli de; http://lattes.cnpq.br/2152513705182408; Oliveira, Milton Adriano Pelli de; Vinaud, Marina Clare; Afonso, Luís Carlos Crocco; Gomes, Clayson Moura; Baeza, Lilian Cristiane
    Leishmania (Viannia) braziliensis is the main species responsible for American tegumentary leishmaniasis in Brazil. However, the use of this parasite species to study Leishmania infection in a murine model has been less conducted when compared to other Leishmania species. Control of murine Leishmania infection has been associated with nitric oxide (NO) produced by inducible NO synthase (iNOS) from M1 macrophage, while arginase expressed by M2 macrophages is related to Leishmania proliferation. The aim of this study was to analyze the ability of L. (V.) braziliensis to proliferate within murine macrophages in vitro for a period of 9 days. Macropha-ges were derived from bone marrow precursors (BMDM) of wild-type mice and were cultured with IFN-γ and LPS, or IL-4, or BMDM iNOS knockout (iNOS KO), and nitric oxide production, arginase activity, and infection with L. (V.) braziliensis. The number of infected macrophages and parasite load were determined by light microscopy. Promastigotes of L. (V.) braziliensis parasites were inoculated (106) into the paw of wild-type and iNOS-deficient mice and lesion progression was measured weekly. Wild-type BMDM were observed to not support proliferation of amastigotes of L. (V.) braziliensis strains after day 3 infection, even within IL-4-treated ma-crophages or iNOS KO macrophages. Arginase activity was higher in iNOS KO macrophages than in IL-4 treated macrophages, showing that the absence of proliferation is arginase inde-pendent. L. (V.) braziliensis was able to cause uncontrolled disease in iNOS KO mice in vivo. The data obtained suggest that murine macrophages do not support proliferation of L. (V.) braziliensis amastigotes, even in the absence of nitric oxide and presence of high arginase ac-tivity. Therefore, further studies related to the requirements of amastigotes internalized in host cells are needed, for the search of better methods to interfere in the diversity of leishmaniasis forms caused by different Leishmania spp.