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Background & Aims The mechanism of action of anti-TNF agents could implicate macrophages modulation in Crohn’s disease (CD). As CD macrophages are defective to control CD-associated adherent-invasive E. coli (AIEC), anti-TNF agents could limit AIEC replication within macrophages. We assessed the effect of anti-TNF agents on AIEC survival within monocytes-derived macrophages (MDM) from CD patients and attempted to identify the implicated proteins. Methods Peripheral blood monocyte-derived macrophages (MDM) were obtained from 44 CD patients including 22 with and 22 without anti-TNF agents. MDM were infected with AIEC-LF82 reference strain. Proteomic analysis was performed before and 6h after AIEC-LF82 infection. Results AIEC-LF82 survival was lower in MDM from CD patients receiving anti-TNF agents compared to those who did not (-73%, p=0.006). After AIEC-LF82 infection, the levels of CD82 (p=0.007), ILF3 (Interleukin enhancer-binding factor 3; p=0.001), FLOT-1 (Flotillin-1; p=0.007) and CHI3L1 (Chitinase 3-like 1; p=0.035) proteins were different within CD-MDM depending on anti-TNF exposure. FLOT-1 (ϱ=- 0.44; p=0.038) and CHI3L1 (ϱ=0.57, p=0.006) levels were inversely and positively correlated with AIEC survival within MDM from CD patients with or without anti-TNF, respectively. We observed a dose-dependent decrease of AIEC-LF82 survival after adjunction of anti-TNF within MDM inducing increase of FLOT-1 and decrease of CHI3L1 mRNA levels. Neutralization of intra-macrophagic CHI3L1 protein using anti-CHI3L1 antibodies reduced AIEC survival within macrophages 6h after infection (p<0.05). Conclusion Anti-TNF agents are able to restrict replication of pathobiont, such as AIEC, within macrophages by modulating FLOT-1 and CHI3L1 expressions in CD patients.
This article aims to inform as guarantee of the Venezuelan immigrants in Brazil. It was sought to address the measles epidemic and the consequences for the region of Roraima. As well as a legal provision requiring due attention to the situation. Measles is a serious infectious and contagious viral disease transmitted by the respiratory system, which mainly affects the malnourished. Brazil was certified as free of disease in 2016. However, in the year 2018, the resurgence of the disease, involving 79 people, including two deaths of children, was reported to the migrant population on the border between Brazil and Venezuela in the state of Roraima.. The state filed with the STF, at the request of refund of entry of immigrants in Brazil. However, there is an infra-constitutional norm that protects the rights of immigrants. In public health, federates in partnership with world health organizations have begun a campaign of mass vaccination of the population of the region in question. From this, it was possible to observe Brazil in order to fulfill its duties with immigration laws and public health in general.
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