Cellular senescence is often considered a protection mechanism triggered by conditions that impose cellular stress. Continuous proliferation, DNA damaging agents or activated oncogenes are well-known activators of cell senescence. Apart from a characteristic stable cell cycle arrest, this response also involves a proinflammatory phenotype known as senescence-associated secretory phenotype (SASP). This, together with the widely known interference with senescence pathways by some oncoviruses, had led to the hypothesis that senescence may also be part of the host cell response to fight virus. Here, we evaluate this hypothesis using vesicular stomatitis virus (VSV) as a model. Our results show that VSV replication is significantly impaired in both primary and tumor senescent cells in comparison with non-senescent cells, and independently of the stimulus used to trigger senescence. Importantly, we also demonstrate a protective effect of senescence against VSV in vivo. Finally, our results identify the SASP as the major contributor to the antiviral defense exerted by cell senescence in vitro, and points to a role activating and recruiting the immune system to clear out the infection. Thus, our study indicates that cell senescence has also a role as a natural antiviral defense mechanism.
In the Brazilian Amazon, the suspected source of infection in an outbreak of acute Chagas disease involving 10 patients was Euterpe oleracea (açaí berry) juice. Patient blood and juice samples contained Trypanosoma cruzi TcIV, indicating oral transmission of the Chagas disease agent.
LPS levels along with the immune consequences of Leishmania infection were associated with elevated cellular activation in coinfected patients. As a consequence, secondary chemoprophylaxis for leishmaniasis or even the use of antiinflammatory drugs or antibiotics may be considered for improving the prognosis of AVL/HIV.
BackgroundChagas disease in the Amazon region is considered an emerging anthropozoonosis with a predominance of the discrete typing units (DTUs) TcI and TcIV. These DTUs are responsible for cases of acute disease associated with oral transmission. Chronic disease cases have been detected through serological surveys. However, the mode of transmission could not be determined, or any association of chronic disease with a specific T. cruzi DTU’s. The aim of this study was to characterize Trypanosoma cruzi in patients with chronic Chagas disease in the State of Amazonas, Brazil.MethodsBlood culture and xenodiagnosis were performed in 36 patients with positive serology for Chagas disease who participated in a serological survey performed in urban and rural areas of Manaus, Amazonas. DNA samples were extracted from the feces of triatomines used for xenodiagnosis, and the nontranscribed spacer of the mini-exon gene and the mitochondrial gene cytochrome oxidase subunit II (COII) were amplified by PCR and sequenced.ResultsBlood culture and xenodiagnosis were negative in 100% of samples; however, molecular techniques revealed that in 13 out of 36 (36%) fecal samples from xenodiagnosis, T. cruzi was characterized as the DTU TcI, and different haplotypes were identified within the same DTU.ConclusionThe DTU TcI, which is mainly associated with acute cases of Chagas disease in the Amazon region, is also responsible for chronic infection in patients from a region in the State of Amazonas.
American tegumentary leishmaniasis (ATL) and human immunodeficiency virus (HIV) are both common infectious diseases in the Brazilian Amazon with overlapping expansion areas, which leads to the occurrence of Leishmania/HIV coinfection. Most ATL/HIV–acquired immunodeficiency syndrome (AIDS) association cases have been reported from areas where Leishmania (Viannia) braziliensis is the main pathogen; this finding is in contrast with the Amazon region, where L. (V.) guyanensis is the most implicated agent, implying distinct clinical and therapeutic aspects. We describe 15 cases of ATL/HIV coinfection treated in a tertiary care center in the Brazilian Amazon between 1999 and 2008. Thirteen patients presented with diverse clinical manifestations of cutaneous leishmaniasis, and four of them had disseminated forms; two patients presented with mucosal leishmaniasis (ML). Seven patients required more than one course of treatment. The particularities of ATL/HIV-AIDS association in L. (V.) guyanensis-endemic areas require efforts for an increased understanding of its burden and subsequent improvements in case management.
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