Interactions Between Candida albicans and Host <br> Interações entre Candida albicans e Hospedeiro

Candida albicans can cause grave infections in patients who are immunocompromised by diseases, by surgery, or by immunesupresive therapy. The high levels of morbidity and mortality resulting from those infections in hospitalized patients show that C. albicans became a prominent human pathogen. Although the host immune system is the major factor balancing the transition from commensalisms to pathogenicity, several virulence attributes expressed by C. albicans, such as adhesion factors, phenotypic switching, dimorphic behavior, and secretion of hydrolytic enzymes, might contribute to the persistence of colonization as well as the development of symptomatic episodes. Host defense against candidiasis relies mainly on the ingestion and elimination of C. albicans by phagocytic cells, which present receptors Toll-like 4, dectin–1 associated to receptors Toll-like2 and mannose receptors. The cytokine IL-10 (IL-10) produced by phagocytes has a crucial role on susceptibility of host fungal infection, whereas IL-10 produced by regulatory T cells is mainly responsible by commensalisms. In contrast, productions of tumour necrosis factor - α (TNF-α), interleukin–1 β (lL-1 β), (IL-6) and (Il-12) provided protective cell–mediated immunity. The interferon-γ produced by natural killer and TH1 cells stimulates migration of phagocytes and major efficacy on destruction of fungi. In epithelial cells from mucosas the NOD-like receptors and defensins-β cytoplasmatic prevent the translocation of C. albicans from microbiota to tissues, which are modulated by IL-1 β, Il-17 and Il-22 cytokines. <p><p> to pathogenicity, several virulence attributes expressed by C. albicans, such as adhesion factors, phenotypic switching, dimorphic behavior, and secretion of hydrolytic enzymes, might contribute to the persistence of colonization as well as the development of symptomatic episodes. Host defense against candidiasis relies mainly on the ingestion and elimination of C. albicans by phagocytic cells, which present receptors Toll-like 4, dectin–1 associated to receptors Toll-like2 and mannose receptors. The cytokine IL-10 (IL-10) produced by phagocytes has a crucial role on susceptibility of host fungal infection, whereas IL-10 produced by regulatory T cells is mainly responsible by commensalisms. In contrast, productions of tumour necrosis factor - α (TNF-α), interleukin–1 β (lL-1 β), (IL-6) and (Il-12) provided protective cell–mediated immunity. The interferon-γ produced by natural killer and TH1 cells stimulates migration of phagocytes and major efficacy on destruction of fungi. In epithelial cells from mucosas the NOD-like receptors and defensins-β cytoplasmatic prevent the translocation of C. albicans from microbiota to tissues, which are modulated by IL-1 β, Il-17 and Il-22 cytokines

Aspirin Modulates Innate Inflammatory Response and Inhibits the Entry of Trypanosoma cruzi in Mouse Peritoneal Macrophages

The intracellular protozoan parasite Trypanosoma cruzi causes Chagas disease, a serious disorder that affects millions of people in Latin America. Cell invasion by T. cruzi and its intracellular replication are essential to the parasite’s life cycle and for the development of Chagas disease. Here, we present evidence suggesting the involvement of the host’s cyclooxygenase (COX) enzyme during T. cruzi invasion. Pharmacological antagonist for COX-1, aspirin (ASA), caused marked inhibition of T. cruzi infection when peritoneal macrophages were pretreated with ASA for 30 min at 37°C before inoculation. This inhibition was associated with increased production of IL-1β and nitric oxide (NO∙) by macrophages. The treatment of macrophages with either NOS inhibitors or prostaglandin E2 (PGE2) restored the invasive action of T. cruzi in macrophages previously treated with ASA. Lipoxin ALX-receptor antagonist Boc2 reversed the inhibitory effect of ASA on trypomastigote invasion. Our results indicate that PGE2, NO∙, and lipoxins are involved in the regulation of anti-T. cruzi activity by macrophages, providing a better understanding of the role of prostaglandins in innate inflammatory response to T. cruzi infection as well as adding a new perspective to specific immune interventions

5-Lipoxygenase deficiency reduces Acetaminophen-Induced hepatotoxicity and lethality

Submitted by Luciane Willcox ([email protected]) on 2016-09-02T15:32:06Z No. of bitstreams: 1 5-Lipoxygenase Deficiency Reduces Acetaminophen-Induced Hepatotoxicity and Lethality.pdf: 2492175 bytes, checksum: 659775e09693604e324165fb1c495a21 (MD5)Approved for entry into archive by Luciane Willcox ([email protected]) on 2016-09-02T15:50:44Z (GMT) No. of bitstreams: 1 5-Lipoxygenase Deficiency Reduces Acetaminophen-Induced Hepatotoxicity and Lethality.pdf: 2492175 bytes, checksum: 659775e09693604e324165fb1c495a21 (MD5)Made available in DSpace on 2016-09-02T15:50:44Z (GMT). No. of bitstreams: 1 5-Lipoxygenase Deficiency Reduces Acetaminophen-Induced Hepatotoxicity and Lethality.pdf: 2492175 bytes, checksum: 659775e09693604e324165fb1c495a21 (MD5) Previous issue date: 2013-10-31This work was supported by grants from SETI/Fundação Araucária, Paraná State Government, Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Coordenadoria de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Patologia. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Patologia. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Patologia. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Patologia. Londrina, PR, Brasil.Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Farmacologia. Ribeirão Preto, SP, Brasil.Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Farmacologia. Ribeirão Preto, SP, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Patologia. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Patologia. Londrina, PR, Brasil / Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Farmacologia. Ribeirão Preto, SP, Brasil.Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Farmacologia. Ribeirão Preto, SP, Brasil.Universidade Estadual de Londrina. Centro de Ciências da Saúde. Departamento de Ciências Farmacêuticas. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Patologia. Londrina, PR, Brasil.5-Lipoxygenase (5-LO) converts arachidonic acid into leukotrienes (LTs) and is involved in inflammation. At present, the participation of 5-LO in acetaminophen (APAP)-induced hepatotoxicity and liver damage has not been addressed. 5-LO deficient (5-LO−/−) mice and background wild type mice were challenged with APAP (0.3–6 g/kg) or saline. The lethality, liver damage, neutrophil and macrophage recruitment, LTB4, cytokine production, and oxidative stress were assessed. APAP induced a dose-dependent mortality, and the dose of 3 g/kg was selected for next experiments. APAP induced LTB4 production in the liver, the primary target organ in APAP toxicity. Histopathological analysis revealed that 5-LO−/− mice presented reduced APAP-induced liver necrosis and inflammation compared with WT mice. APAP-induced lethality, increase of plasma levels of aspartate aminotransferase and alanine aminotransferase, liver cytokine (IL-1β, TNF-α, IFN-γ, and IL-10), superoxide anion, and thiobarbituric acid reactive substances production, myeloperoxidase and N-acetyl-β-D-glucosaminidase activity, Nrf2 and gp91phox mRNA expression, and decrease of reduced glutathione and antioxidant capacity measured by 2,2′-azinobis(3-ethylbenzothiazoline 6-sulfonate) assay were prevented in 5-LO−/− mice compared to WT mice. Therefore, 5-LO deficiency resulted in reduced mortality due to reduced liver inflammatory and oxidative damage, suggesting 5-LO is a promising target to reduce APAP-induced lethality and liver inflammatory/oxidative damage