O papel do IFN- na infecção por Leishmania amazonensis

Exportado OPUSMade available in DSpace on 2019-08-10T17:48:34Z (GMT). No. of bitstreams: 1 disserta__o_matheus_1_revisada.pdf: 1337008 bytes, checksum: 20c7e759936bb9ac8c8c8861c0191f38 (MD5) Previous issue date: 30O IFN-ã é uma citocina chave para a proteção frente à infecção por uma série de parasitos intracelulares, tais quais: Leishmania major, Toxoplasma gondii, Trypanosoma cruzi, Plasmodium chabaudi e Mycobacterium tuberculosis. O mecanismo pelo qual esta citocina atua se dá pela ativação clássica de macrófagos, que passa a expressar iNOS, gerando a produção de NO, que leva à morte destes parasitos. A importância desta citocina, in vivo e in vitro, já está bem estabelecida para os modelos de infecção citados. Curiosamente, o mesmo não ocorre para infecção por L. amazonensis. Neste caso, foi demonstrado que, in vitro, a forma amastigota do parasito é estimulada a proliferar na presença de IFN-ã. Além disso, a relevância desta citocina para a proteção, in vivo, parece ocorrer apenas nos tempos finais da infecção. O mecanismo pelo qual o IFN-ã não é essencial nos tempos iniciais da infecção ainda não é entendido. Desta forma, constituiu objetivo do nosso trabalho entender o papel do IFN-ã na infecção in vivo pela cepa PH8. Além disso, a elucidação do real papel do IFN-ã é essencial para os estudos que visam a produção de uma vacina eficaz. Nossos dados confirmam a importância do IFN-ã apenas nos tempos finais da infecção, como já descrito para outras cepas de L. amazonensis. O mecanismo pelo qual camundongos IFN-ã -/- não exibem maior suscetibilidade após 10 semanas de infecção parece ser dependente de um balanço entre expressão de arginase I e iNOS; além de modulação de IL-10. Apesar deste papel restrito ao final da infecção, o IFN-ã é essencial para imunização por Leishvacin, em mecanismo dependente da expressão de iNOS. Nossos dados indicam a importância desta citocina para o controle parcial da infecção por L. amazonensis, e também para a imunização, mas sugere a possibilidade de que outros fatores, ainda desconhecidos, possam ser importantes para o controle da infecção no seu início, e também para a geração de imunidade.IFN-ã is a key cytokine for protection against many infections caused by a number of intracellular parasites, such as: Leishmania major, Toxoplasma gondii, Trypanosoma cruzi, Plasmodium chabaudi and Mycobacterium tuberculosis. The mechanism by which this cytokine acts is the classical activation of macrophages that expresses iNOS, leading to production of NO, which leads to death of these parasites. The importance of this cytokine in vivo and in vitro is already well established for the models of infection cited. Surprisingly, the same is not true for infection by L. amazonensis. In this case, it was demonstrated that, in vitro, the amastigotes of the parasite are stimulated to proliferate in the presence of IFN-ã. Moreover, the relevance of this cytokine for protection in vivo occurs only in the later times of infection. The mechanism by which IFN-ã is not essential in the initial days of infection is still not understood. Thus, the aim of our study was to investigate the role of IFN-ã during in vivo infection by the strain PH8. Furthermore, the elucidation of the real role of IFN-ã is essential for studies that aim to produce an effective vaccine. Our data confirm the importance of IFN-ã only in the later times of infection, as described for other strains of L. amazonensis. The mechanism by which IFN-ã -/- mice do not exhibit increased susceptibility to infection after 10 weeks appears to be dependent on a balance between expression of arginase I and iNOS, in addition to modulation of IL-10. Despite this limited role at the end of the infection, IFN-ã is essential for immunization by Leishvacin, in a mechanism-dependent of iNOS expression. Our data indicate the importance of this cytokine for the partial control of infection by L. amazonensis, and also for immunization, but suggests the possibility that other factors, still unknown, may be important for infection control in the beginning, and also for the generation of immunity

Site-dependent recruitment of inflammatory cells determines the effective dose of leishmania major

Submitted by Rodrigo Senorans ([email protected]) on 2015-06-17T18:13:19Z No. of bitstreams: 1 Site-Dependent Recruitment of Inflammatory Cells Determines the.pdf: 4547942 bytes, checksum: a0c07295ddd9aca2f1ca951279b7bebb (MD5)Approved for entry into archive by Anderson Silva ([email protected]) on 2015-06-18T14:15:53Z (GMT) No. of bitstreams: 1 Site-Dependent Recruitment of Inflammatory Cells Determines the.pdf: 4547942 bytes, checksum: a0c07295ddd9aca2f1ca951279b7bebb (MD5)Approved for entry into archive by Anderson Silva ([email protected]) on 2015-06-18T14:16:40Z (GMT) No. of bitstreams: 1 Site-Dependent Recruitment of Inflammatory Cells Determines the.pdf: 4547942 bytes, checksum: a0c07295ddd9aca2f1ca951279b7bebb (MD5)Made available in DSpace on 2015-06-18T18:35:21Z (GMT). No. of bitstreams: 1 Site-Dependent Recruitment of Inflammatory Cells Determines the.pdf: 4547942 bytes, checksum: a0c07295ddd9aca2f1ca951279b7bebb (MD5) Previous issue date: 2014NIH-CAPESNational Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Bethesda, MD, USA.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Imunologia e Imunogenética em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil / National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Bethesda, MD, USA / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Laboratório de Gnotobiologia e Imunologia. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil.National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Bethesda, MD, USA / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Laboratório de Gnotobiologia e Imunologia. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil.National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Bethesda, MD, USA.National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Bethesda, MD, USA.National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Bethesda, MD, USA.The route of pathogen inoculation by needle has been shown to influence the outcome of infection. Employing needle inoculation of the obligately intracellular parasite Leishmania major, which is transmitted in nature following intradermal (i.d.) deposition of parasites by the bite of an infected sand fly, we identified differences in the preexisting and acute cellular responses in mice following i.d. inoculation of the ear, subcutaneous (s.c.) inoculation of the footpad, or inoculation of the peritoneal cavity (intraperitoneal [i.p.] inoculation). Initiation of infection at different sites was associated with different phagocytic populations. Neutrophils were the dominant infected cells following i.d., but not s.c. or i.p., inoculation. Inoculation of the ear dermis resulted in higher frequencies of total and infected neutrophils than inoculation of the footpad, and these higher frequencies were associated with a 10-fold increase in early parasite loads. Following inoculation of the ear in the absence of neutrophils, parasite phagocytosis by other cell types did not increase, and fewer parasites were able to establish infection. The frequency of infected neutrophils within the total infected CD11b+ population was higher than the frequency of total neutrophils within the total CD11b+ population, demonstrating that neutrophils are overrepresented as a proportion of infected cells. Employing i.d. inoculation to model sand fly transmission of parasites has significant consequences for infection outcome relative to that of s.c. or i.p. inoculation, including the phenotype of infected cells and the number of parasites that establish infection. Vector-borne infections initiated in the dermis likely involve adaptations to this unique microenvironment. Bypassing or altering this initial step has significant consequences for infection

The Multifaceted Role of Commensal Microbiota in Homeostasis and Gastrointestinal Diseases

The gastrointestinal tract houses a complex and diverse community of microbes. In recent years, an increased understanding of the importance of intestinal microbiota for human physiology has been gained. In the steady state, commensal microorganisms have a symbiotic relationship with the host and possess critical and distinct functions, including directly influencing immunity. This means that recognition of commensal antigens is necessary for the development of complete immune responses. Therefore, the immune system must face the challenge of maintaining mucosal homeostasis while dealing with undue passage of commensal or pathogenic microbes, as well as the host nutritional status or drug use. Disruption of this fine balance has been associated with the development of several intestinal inflammatory diseases. In this review, we discuss the mechanisms involved in the modulation of host-microbe interactions and how the breakdown of this homeostatic association can lead to intestinal inflammation and pathology

Short-term protection conferred by Leishvacin® against experimental Leishmania amazonensis infection in C57BL/6 mice.

To date, there is no vaccine available against human leishmaniasis. Although some vaccination protocols can induce immunity in murine models, they fail to induce protection in humans. The reasons for that remain unclear. The aimof the present study was to characterize the changes in the pattern of the immune response during subcutaneous vaccination with Leishvacin® in mice. We also investigated whether IFN-γ and nitric oxide synthase are indispensable for the protection elicited by the vaccine. C57BL/6 WT vaccinated mice showed smaller lesions and fewer numbers of parasites in footpads until 8 weeks post-infection. Up to this time, they produced higher levels of IFN-γ, IL-2, IL-4, IL-17A and IL-10 and higher specific antibody response than control non-vaccinated mice. Moreover, we showed that IFN-γ, most likely by induction of iNOS expression, is essential for immunity. However, after 12 weeks of infection, we observed loss of difference in lesion size and parasite burden between the groups. Loss of resistancewas associatedwith the disappearance of differences in cytokine patterns between vaccinated and control mice, but not of antibody response, which remained different until a later time of infection. The reversal of resistance to L. amazonensis could not be explained by upregulation of regulatory cytokines. Our data point to a subversion of the host immune response by L. amazonensis even when a protective response was previously induced

Low and high-dose intradermal infection with Leishmania majorand Leishmania amazonensis in C57BL/6 mice

A model of skin infection with Leishmania amazonensiswith low doses of parasites is compared to infection with high doses of L. amazonensis and low and high doses of Leishmania major. C57BL/6 mice were infected with 10³ or 10(6) parasites in the ear and the outcome of infection was assessed. The appearance of lesions in mice infected with 10³ parasites was delayed compared to mice infected with 10(6) Leishmania and parasites were detectable at the infection site before lesions became apparent. Mice infected with L. amazonensisdisplayed persistent lesions, whereas infection with L. major spontaneously healed in all groups, although lymphocytes persisted at the site of infection after healing. Macrophages persisted only in L. amazonensis-infected mice. High-dose L. amazonensis-infected mice produced lower levels of IFN-γ and TNF than mice infected with L. major. No correlation between the persistence of parasites and IL-10 levels and the production of nitric oxide or urea by macrophages was found. We conclude that infection with low doses of L. amazonensisin the dermis changes the course of infection by delaying the appearance of lesions. However, low-dose infection does not change the outcomes of susceptibility and cytokine production described for subcutaneous infection with high numbers of parasites

Characterisation of microbial attack on archaeological bone

As part of an EU funded project to investigate the factors influencing bone preservation in the archaeological record, more than 250 bones from 41 archaeological sites in five countries spanning four climatic regions were studied for diagenetic alteration. Sites were selected to cover a range of environmental conditions and archaeological contexts. Microscopic and physical (mercury intrusion porosimetry) analyses of these bones revealed that the majority (68%) had suffered microbial attack. Furthermore, significant differences were found between animal and human bone in both the state of preservation and the type of microbial attack present. These differences in preservation might result from differences in early taphonomy of the bones. © 2003 Elsevier Science Ltd. All rights reserved