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MSc (Med) Molecular Medicine and Haematology, Faculty of Health Sciences, University of the Witwatersrand / In recent years there has been much progress in understanding and defining the key protein structure-function relationships that mediate Human Immunodeficiency Virus (HIV-1) entry into host CD4+ cells. This process involves fusion of the virus and host cell membranes, following engagement of corresponding viral (gp120) and target (CD4) receptor proteins. Binding of gp120 to CD4 triggers extensive conformational changes in gp120, exposing binding sites for the co-receptor proteins (CCR5 or CXCR4), and facilitating insertion of gp41, the viral fusion protein, into the target cell membrane. Following insertion of gp41, oligomerisation of fusogenic domains on gp41 is thought to drive the juxtaposition of the virus and host cell and fusion of their membranes. Recent reports suggest that detergent-resistant membrane domains, known as lipid rafts, play a crucial role in orientating the receptor molecules during this step of HIV-1 infection. Lipid rafts are typically rich in cholesterol, sphingolipids and GPI-anchored proteins, and are biophysically distinct from the glycerophosolipid bilayer, which constitutes the bulk of mammalian cell membranes. The role of lipid rafts in virus entry, however, is still controversial, and further experimentation is needed to define their importance in this regard. To provide insight into the role of lipid rafts during HIV-1 entry, we evaluated the natural distribution of the host receptor proteins in HIV-1 target cells (U87.CD4.CCR5/CXCR4). CD4 was detected in membrane samples fractionated by sucrose density gradient centrifugation using immunoblotting techniques, while CCR5 and CXCR4 were detected on whole cells by fluorescence microscopy. We then used a primary CCR5-utilising subtype C HIV-1 isolate (FV5) to characterise dynamic changes in the distribution of these receptors and gp41 during viral entry in real-time. Viral fusion assays were set up by inoculating v target cells with FV5 at 23 ºC, a temperature that allows HIV-1 attachment, but is nonpermissive for advancement of the fusion reaction. This prefusogenic form of the virus-host receptor complex is defined as the temperature-arrested state (TAS). We found that, under normal, uninfected conditions, CD4, CCR5 and CXCR4 are distributed throughout both raft and non-raft microdomains on the U87 cell surface, and there is little evidence for any significant redistribution of these receptors into lipid rafts during the HIV-mediated fusion reaction. Interestingly, we observed a change in the structure of CD4 during the fusion process, which could describe a functionally important event in HIV-1 entry, or be related to compromises in the integrity of the virally-infected membranes. Moreover, we discovered that gp41 is capable of membrane insertion and oligomerisation at TAS, in contrast to previous reports that suggest the fusion peptide is not capable of breaching the membrane at this temperature. Our results provide valuable novel insights into the HIV-1 subtype C entry process, and the involvement of lipid rafts in this stage of the viral lifecycle, that may be relevant to novel therapy and immunogen design.

Les lymphocytes T CD4+ auxiliaires ou T helper en anglais sont capables de soutenir une grande diversité de fonctions grâce à leur capacité à se différencier en différents sous-types effecteurs en fonction de l’antigène rencontré et de l’environnement cytokinique dans lequel ils se trouvent. Les connaissances actuelles sur la différenciation des cellules T helper mettent en avant l’existence de réseaux transcriptionnels particulièrement complexes et spécifiques à chaque sous-ensemble T helper. En 2008, les cellules T CD4 sécrétrices d’IL-9 (Th9) sont identifiées comme un nouveau sous-type de cellules T helper. Différenciées en présence d’IL-4 et TGF-β, les cellules Th9 sécrètent de l’IL-9 et de l’IL-21, et contribuent au développement de maladies auto-immunes et allergiques. Les lymphocytes Th9 présentent également des propriétés anti-tumorales particulièrement intéressantes.Le réseau transcriptionnel des cellules Th9 résulte d’un équilibre entre les voies de signalisation induites par les différentes cytokines nécessaires à sa polarisation. L’IL-4 permet l’activation de STAT6 et l’expression de GATA3 et IRF4, tandis que le TGF-β conduit à l’activation de la voie des Smad et l’expression du facteur PU.1. Le module transcriptionnel IRF4/BATF ainsi que le facteur PU.1 sont des messagers indispensables au développement des cellules Th9 et à la sécrétion d’IL-9.IRF8 est un facteur de transcription critique pour le développement des cellules myéloïdes et des lymphocytes B. Récemment, il est apparu qu’IRF8 était impliqué dans la polarisation de sous-ensembles T helper. En effet, IRF8 limite la sécrétion d’IL-17 par les cellules Th17, de même qu’il réprime l’expression de l’Il4 et l’Il17 dans les cellules Treg. Structurellement proche d’IRF4, IRF8 interagit avec des cofacteurs tels que PU.1 ou BATF afin de réguler l’activité transcriptionnelle.Ce travail présenté ici révèle que le facteur IRF8 participe à la polarisation des cellules Th9 in vitro et in vivo. Le TGF-β nécessaire à la différenciation des cellules Th9 régule directement l’expression d’Irf8 grâce à l’activation de Smad3. Comme dans d’autres types cellulaires, la fonction transcriptionnelle d’IRF8 est dépendante de ces partenaires d’interaction. Nous montrons qu’en présence des facteurs PU.1, IRF4 et BATF, IRF8 participe à un complexe multiprotéique nécessaire à l’induction des cytokines caractéristiques des cellules Th9, notamment l’Il9 et l’Il21. Nous démontrons également qu’en présence de la protéine ETV6, IRF8 est capable de former un complexe initiant la répression de l’activité transcriptionnelle de l’Il4. Nous soulignons ainsi le rôle bivalent joué par IRF8 dans le développement des cellules Th9 dépendamment de ses partenaires. Pour finir, l’expression d’Irf8 est nécessaire aux cellules Th9 pour exercer leurs fonctions anti-tumorales. / CD4 helper T cells support a wide range of functions due to their ability to differentiate into different effector subsets depending on the antigen encountered and the cytokine environment in which they are. Current knowledge on the differentiation of helper T cells highlights the existence of complex transcriptional networks specific to each T helper subset. In 2008, IL-9 secreting CD4 T cells (Th9) are identified as a new helper T cell subtype. Differentiated in the presence of IL-4 and TGF-β, Th9 cells secrete IL-9 and IL-21, and contribute to the development of autoimmune and allergic diseases. Th9 lymphocytes also exhibit strong anti-tumor properties.The transcriptional network of the Th9 cells results from a balance between the signaling pathways induced by the different cytokines required for its polarization. IL-4 allows activation of STAT6 and expression of GATA3 and IRF4, whereas TGF-β leads to activation of the Smad pathway and expression of the transcription factor PU.1. The IRF4 / BATF transcriptional module and the PU.1 factor are essential messengers for the development of Th9 cells and IL-9 secretion.IRF8 is a crucial transcription factor for the development of myeloid cells and B lymphocytes. Recently it appeared that IRF8 was involved in helper T subset polarization. Indeed, IRF8 limits the secretion of IL-17 by Th17 cells, as well as repressing the expression of Il4 and Il17 in Treg cells. Structurally close to IRF4, IRF8 interacts with cofactors such as PU.1 or BATF in order to regulate transcriptional activity.This work reveals that the IRF8 transcription factor contributes to the polarization of Th9 cells in vitro and in vivo. The TGF-β needed for Th9 cell differentiation activate Smad3 pathway which directly modulates the Irf8 expression. As in many cellular subtypes, the transcriptional function of IRF8 is dependent on these interaction partners. We show that in the presence of the transcription factors PU.1, IRF4 and BATF, IRF8 participates in a multiprotein complex essential for the induction of the Th9 cytokines, Il9 and Il21. We also demonstrate that in the presence of the ETV6 protein, IRF8 is able to form a complex responsible for the repression of Il4 expression. We underline the bivalent role played by IRF8 in the development of Th9 cells depending on its partners. Finally, expression of Irf8 is crucial for Th9 cells to exercise their antitumor functions.

Made available in DSpace on 2014-06-11T19:31:11Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-01-19Bitstream added on 2014-06-13T20:22:02Z : No. of bitstreams: 1 faria_jlm_dr_jabo.pdf: 2769905 bytes, checksum: 15c4be53d67c11751ac4644728993d4f (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A infecção aguda experimental pela amostra Jaboticabal de Ehrlichia canis provoca alterações clínicas severas no hospedeiro, com graves distúrbios sanguíneos e imunológicos, que podem comprometer a vida do animal. Com este estudo buscou-se avaliar a expressão gênica de TNF-α, IFN-γ e IL-10, pesquisar a presença de mórulas no baço e avaliar o imunofenótipo das células esplênicas antes, nos dias 6, 18 e 30 após a inoculação e 25 dias após o tratamento com cloridrato de doxicilina, em cinco cães sem definição racial inoculados com a amostra Jaboticabal de Ehrlichia canis. Nas condições experimentais desta pesquisa, o início do desenvolvimento dos sinais clínicos, seis dias após a inoculação (D6) foi acompanhado pela expressão de TNF-α e aumento de células MHC II+ (P<0,05) na citologia esplênica em relação ao controle. Com o desenvolvimento da infecção experimental (D18) ocorreu o agravamento dos sinais clínicos, os cães apresentaram febre, linfadenomegalia e esplenomegalia acompanhados de trombocitopenia, leucopenia e anemia, mórulas na citologia esplênica, aumento significativo da expressão de TNF-α em leucócitos e células esplênicas, detecção de IL-10, tanto em leucócitos como em células esplênicas e redução de células CD4+ (P<0,05), em relação ao momento anterior e ao grupo controle, macrófagos (P<0,05) em relação ao controle, e aumento de células B (P<0,05) em relação a D-1 e ao grupo controle. Aos 30 dias os cães já não apresentavam sinais clínicos da infecção, porém persistia a trombocitopenia. Além disso, persistência do aumento das células B+ esplênicas (P<0,05), diminuição significativa das células CD4+ e dos macrófagos em relação ao D18 e ao controle. O TNF-α atingiu sua maior taxa de expressão e ocorreu a detecção de IFN-γ. / The experimental acute infection by Ehrlichia canis Jaboticabal sample provokes severe clinical alterations in the host with serious blood and immunological disorders that may compromise the animal’s life. The present study aimed to evaluate the gene expression of TNF-α, IFN-γ and IL-10, search morulae presence in the spleen and evaluate the splenic cells’ immunophenotype before, at days 6, 18 and 30 days post inoculation and 25 days after the treatment with doxycycline cloridrate, in five cross-bred dogs inoculated with Ehrlichia canis Jaboticabal sample. At the experimental conditions of this research, the beginning of the development of the clinical signs, six days after the inoculation (D6) was accompanied by expression of TNF-α and increase of MHC II+ cells (P<0,05) at the splenic cytology when compared to the control group. As long as the experimental infection was developed (D18) the clinical signs were becoming worse, the dogs presented fever, lymphadenomegalia and spleenomegalia accompanied by thrombocytopenia, leucopenia and anemia, morulae in the splenic cytology, significant increase of the expression of TNF-α in leukocytes and splenic cells, detection of IL-10 both in leukocytes and in splenic cells and the decrease of CD4+ cells (P<0,05) in comparison to the previous moment and to the control group, macrophages (P<0,05) compared to the control group, and increase of cells B (P<0,05) in comparison to the control group and D-1. At day 30 the dogs no more presented the infection clinical signs, although the thrombocytopenia persisted. Besides, persistent splenic cells B+ increase (P<0,05), significant reduction of CD4+ cells and macrophages compared to D18 and to the control group were observed. The TNF-α reached its highest expression rate and the detection of IFN-γ ocurred.

Orientador: Mirela Tinucci Costa / Banca: Aguemi Kohayagawa / Banca: Tiago Wilson Patriarca Mineo / Banca: Rosangela Zacarias Machado / Banca: Aureo Evangelista Santana / Resumo: A infecção aguda experimental pela amostra Jaboticabal de Ehrlichia canis provoca alterações clínicas severas no hospedeiro, com graves distúrbios sanguíneos e imunológicos, que podem comprometer a vida do animal. Com este estudo buscou-se avaliar a expressão gênica de TNF-α, IFN-γ e IL-10, pesquisar a presença de mórulas no baço e avaliar o imunofenótipo das células esplênicas antes, nos dias 6, 18 e 30 após a inoculação e 25 dias após o tratamento com cloridrato de doxicilina, em cinco cães sem definição racial inoculados com a amostra Jaboticabal de Ehrlichia canis. Nas condições experimentais desta pesquisa, o início do desenvolvimento dos sinais clínicos, seis dias após a inoculação (D6) foi acompanhado pela expressão de TNF-α e aumento de células MHC II+ (P<0,05) na citologia esplênica em relação ao controle. Com o desenvolvimento da infecção experimental (D18) ocorreu o agravamento dos sinais clínicos, os cães apresentaram febre, linfadenomegalia e esplenomegalia acompanhados de trombocitopenia, leucopenia e anemia, mórulas na citologia esplênica, aumento significativo da expressão de TNF-α em leucócitos e células esplênicas, detecção de IL-10, tanto em leucócitos como em células esplênicas e redução de células CD4+ (P<0,05), em relação ao momento anterior e ao grupo controle, macrófagos (P<0,05) em relação ao controle, e aumento de células B (P<0,05) em relação a D-1 e ao grupo controle. Aos 30 dias os cães já não apresentavam sinais clínicos da infecção, porém persistia a trombocitopenia. Além disso, persistência do aumento das células B+ esplênicas (P<0,05), diminuição significativa das células CD4+ e dos macrófagos em relação ao D18 e ao controle. O TNF-α atingiu sua maior taxa de expressão e ocorreu a detecção de IFN-γ. / Abstract: The experimental acute infection by Ehrlichia canis Jaboticabal sample provokes severe clinical alterations in the host with serious blood and immunological disorders that may compromise the animal's life. The present study aimed to evaluate the gene expression of TNF-α, IFN-γ and IL-10, search morulae presence in the spleen and evaluate the splenic cells' immunophenotype before, at days 6, 18 and 30 days post inoculation and 25 days after the treatment with doxycycline cloridrate, in five cross-bred dogs inoculated with Ehrlichia canis Jaboticabal sample. At the experimental conditions of this research, the beginning of the development of the clinical signs, six days after the inoculation (D6) was accompanied by expression of TNF-α and increase of MHC II+ cells (P<0,05) at the splenic cytology when compared to the control group. As long as the experimental infection was developed (D18) the clinical signs were becoming worse, the dogs presented fever, lymphadenomegalia and spleenomegalia accompanied by thrombocytopenia, leucopenia and anemia, morulae in the splenic cytology, significant increase of the expression of TNF-α in leukocytes and splenic cells, detection of IL-10 both in leukocytes and in splenic cells and the decrease of CD4+ cells (P<0,05) in comparison to the previous moment and to the control group, macrophages (P<0,05) compared to the control group, and increase of cells B (P<0,05) in comparison to the control group and D-1. At day 30 the dogs no more presented the infection clinical signs, although the thrombocytopenia persisted. Besides, persistent splenic cells B+ increase (P<0,05), significant reduction of CD4+ cells and macrophages compared to D18 and to the control group were observed. The TNF-α reached its highest expression rate and the detection of IFN-γ ocurred. / Doutor

This study examined strategies that can be used for bringing about HIV/AIDS awareness in primary schools. The strategies are effective teaching skills that can be employed by educators for bringing HIV/AIDS awareness to primary school learners. The responsibilities of educators in the implementation of HIV/AIDS programs in primary schools were discussed. It was noted that educators have a great responsibility of teaching learners about HIV/AIDS, the most important of which was to provide learners with accurate information regarding HIV/AIDS. Another one was that educators should also make sure that effective teaching and learning of HIV/AIDS does takes place in the schools. The study has also examined knowledge that children should have regarding the HIV/AIDS epidemic. The basic awareness of HIV/AIDS by children was found to be essential. Some of the factors that promote the spread of HIV infection were also discussed. Different types of STIs were discussed. From the discussions, it is evident that there is a link between STIs and HIV/AIDS. Although STIs can be treated by medication, they are sometimes hard to cure. In this study, it was discovered that the early and correct treatment of STIs is an important weapon in the armoury against HIV transmission. The significance of life skills programs in primary schools was also examined. It was discovered that the subject of HIV/AIDS could not be taught in isolation; life skills programs should always be included. The issue of primary school learners who are infected and affected by HIV/AIDS was also discussed. It was discovered that in the context of HIV/AIDS, learners fall into two main groups, namely the infected and affected. Infected learners are those learners who are living with the virus in their bodies, while affected learners are those who have infected family members or friends. Various ways by which HIV can be transmitted and prevented in primary schools were also examined. Strategies that can be used for bringing about HIV/AIDS awareness in primary schools were dealt with in chapter six. Recommendations based on teaching skills that can be used by educators in presenting HIV/AIDS lessons were made. / Dissertation (Magister Educationis (Learners Support, Guidance and Counselling))--University of Pretoria, 2006. / Educational Psychology / unrestricted

L’échappement des tumeurs à la surveillance du système immunitaire est une des raisons pour lesquelles le cancer parvient à se développer. Un des objectifs de notre équipe consiste à étudier les lymphocytes T CD4+ et leurs rôles dans un contexte de cancer. Mon travail de thèse a eu pour objectif de déterminer si les résultats murins obtenus au laboratoire étaient transposables à l’Homme, et surtout dans le cancer du sein. Nous avons tout d’abord mis en évidence que les lymphocytes Th17 infiltrant les cancers du sein inhibent les fonctions effectrices des lymphocytes T cytotoxiques de manière dépendante des ectonucléotidases. Enfin, nous avons montré qu’une infiltration tumorale riche en cellules Th17 est associée à un moins bon pronostic clinique des patientes atteintes de cancer du sein. Nous avons ensuite eu pour objectif de tenter de limiter la différenciation de ces cellules Th17. Nous avons démontré que l’activation de SIRT1 diminue l’acétylation de STAT3 ce qui perturbe le programme de différenciation de ces cellules. L’activation de SIRT1 in vivo limite l’expansion des Th17 et conduit à un ralentissement de la croissance tumorale. Ce concept fut validé chez l’Homme et ouvre donc la possibilité d’association d’agonistes de SIRT1 avec la chimiothérapie. Le dernier projet porte sur les lymphocytes Th9 et leur rôle pronostique dans le cancer du sein. Nous avons mis en évidence que les propriétés effectrices des lymphocytes Th9 humains pouvaient être augmentées par l’IFNα via l’activation du facteur de transcription IRF1. Nous avons enfin démontré que l’infiltration tumorale de lymphocytes Th9 était associée au meilleur pronostic des patientes. / Tumor escape to immune system surveillance is one of the reasons why human cancer achieves to grow. In my research team, we aim to study CD4 T cell populations and their functions in the context of cancer. My work was precisely to determine if the results obtained in mice could be transposable in humans, in the context of breast cancer. . We first unraveled that tumor infiltrating Th17 cells could inhibit effector and cytotoxic functions of Th1 and CD8 T cells in an ectonucleotidase-dependent manner. Finally, we showed that high tumor infiltration in IL-17+ cells were significantly associated with a worse clinical prognosis for breast cancer patients. Then, we aim to prevent Th17 cell differentiation. We first established that SIRT1 activation reduces STAT3 acetylation thus limiting Th17 cell differentiation. Activation of SIRT1 limits in vivo Th17 cell expansion and leads to the decrease of tumor growth. This concept has been validated in humans and gives the possibility to associate SIRT1 agonists with chemotherapy. The last project concerns the role and the prognosis impact of Th9 lymphocytes in breast cancer. We highlighted that the effector properties of human Th9 cells could be increased by IFNα via IRF1 activation. Finally, we attested that the tumor infiltration of Th9 lymphocytes was associated with a better prognosis for breast cancer patients.

The immune system is a complex network of tissues, cells and proteins which protects us against infections and invading pathogens we encounter every day. Immunosenescence refers to age-related impairments in immune function which may contribute to increased prevalence and severity of infectious disease in the elderly. How and why ageing affects the immune system is not fully understood. Using a naturally aged mouse model, work in this thesis shows that the abundance of a rare type of lymphocyte, known as NKT cells, increased across multiple immune organs. Additionally, macrophage abundance was also altered in the lymph nodes of aged mice. Invariant NKT (iNKT) cells express an invariant T cell receptor (TCR) which recognises lipids presented on the CD1d molecule. iNKT cells can be activated and respond to invading pathogens either by recognition of antigens through TCR-CD1d interactions or cytokine-dependent means. Less is known about NKT-like cells, which also express NK cell-associated surface markers, such as CD49b, but lack an invariant TCR. Data within this thesis show that both iNKT and NKT-like cell populations are abundant in the spleen and liver of aged mice. iNKT and NKT-like cells can be divided into subpopulations based on their expression of surface markers or transcription factors, and data suggests that not all subpopulations of these cells are affected by age equally. For instance, flow cytometry showed that while spleen-derived iNKT cells are significantly increased in aged mice, within the iNKT cell population the percentage representation of CD4+ cells are significantly reduced with age. Additionally, data indicates that both iNKT and NKT-like cells from aged mice show compromised responses to in vitro stimulation compared to young controls. Using bone marrow chimeras, where either young cells are reconstituted within an aged mouse or old cells are reconstituted within a young mouse, provided the opportunity to determine whether the aged environment contributes to this diminished response. Data demonstrates that the aged environment plays at least a partial role in these age-related changes to response to stimulation, however the young environment seems unable to reverse these changes. Macrophages are phagocytes which are found within all organs of the body. Studies in this thesis show that CD169+ macrophages have diminished numbers in the lymph nodes of aged mice, but this did not seem to affect the capture of the model antigen, dextran. Further studies revealed ageing affects macrophage populations differently in the different tissues within the body. For example, macrophage numbers remain constant in the spleen with ageing, but appear to increase in density in the lungs. To conclude, ageing can cause dramatic changes to the numbers and function of different cells of the immune system across multiple organs. Furthering our understanding of the ageing immune system and the underlying mechanisms which cause age-related decline in immune function is important to design strategies to improve the quality of the lives of the elderly.

Viral protein r (Vpr) of Human immunodeficiency virus type 1 (HIV-1) plays an important role in the ability of the virus to infect cells and cause disease. Two polymorphisms to Vpr have been shown to result in differences in disease progression in infected individuals. R36W tends to result in rapid disease progression while R77Q results in long-term non-progression. In order to better understand how these polymorphisms result in these different disease phenotypes, our lab has recently shown that in cell culture, the R36W polymorphism results in increased viral replication and greater induction of cell death. On the other hand, infection with R77Q results in increased G2 cell cycle arrest and increased induction of apoptosis. In this thesis, we have attempted to study how these two polymorphisms affect the ability of HIV-1 to cause cell death in primary CD4+ cells. We show that infection by a Vpr knockout virus results in increased apoptosis while infection with R77Q and R36W result in decreased apoptosis. Additionally, R77Q infection results in increased p24 production. Further, we attempted create a Rag2-/- γc-/- humanized mouse model in order to better study roles of these polymorphisms in vivo. An additional goal of this thesis was to characterize twelve novel Bacillus anthracis bacteriophage. B. anthracis is gram positive, anaerobic, rod best known for being the causative agent of anthrax. Bacteriophage, viruses that infect bacteria, have been used to identify bacterial contamination and to treat infection. Herein, we report the isolation, sequencing, and characterization of twelve novel phages that infect B. anthracis. The genomes were annotated using DNA Master and BLASTp. Hypothetical proteins were analyzed with Phyre2 to predict possible functions based on protein structure, revealing over 100 new predicted functions. Dotplot generation showed that these phages group into four distinct clusters. By running the major portal protein of one representative of each cluster through BLASTp, we have identified the closest relatives to our novel phages and placed them into their respective genera and groups.

Mais de 2 bilhões de pessoas em todo o mundo encontram-se infectadas com Toxoplasma gondii. Na região endêmica de Erechim, RS, cerca de 90% da população é soropositiva e cerca de 18% destes indivíduos apresentam lesões oculares com manifestações clínicas. A estrutura genética das populações do T. gondii tem sido bastante investigada, a despeito da infecção ter se espalhado pelo mundo, do grande número de hospedeiros intermediários e da capacidade do parasita de se reproduzir sexualmente. Linhagens de T. gondii com atípica ou nova combinação de alelos têm sido isoladas de animais não domésticos ou em outros continentes, como América do Sul e África, e de pacientes com apresentações clínicas incomuns. Em modelos murinos, as linhagens com o genótipo tipo I são altamente virulentas, em contraste às cepas tipo II e tipo III que são menos virulentas. Este trabalho propõe a caracterização fenotípica da resposta imune do hospedeiro frente a infecção por diferentes cepas de T. gondii, bem como o isolamento e a caracterização genotípica das linhagens de T. gondii que infectam indivíduos de Erechim no Rio Grande do Sul. Para a caracterização fenotípica utilizamos duas cepas de T. gondii já bem estabelecidas, a cepa RH (tipo I) e a ME49 (tipo II), e uma cepa isolada a partir de gatos domésticos do Brasil, chamada TgCatBr71. Sendo assim, através da fenotipagem das células dendríticas de camundongos C57Bl/6 infectados com as cepas citadas, foi possível observar que essas cepas induzem expressão das moléculas de superfície CD40, CD80, CD86 e MHC classe II em DCs CD11c+, porém sem significativa diferença entre as cepas. Com relação as células CD4+ e células CD8+, observamos o aumento das células CD8+ no decorrer da infecção pelas cepas RH e ME49, indicando a importância deste tipo celular na resposta protetora contra T. gondii. Avaliamos também a produção de citocinas IL-12, IFN-g e IL-10 em células esplênicas de camundongos infectados pelas três cepas no decorrer da infecção e detectamos que camundongos infectados pela cepa tipo II (ME49) apresentam síntese maior dessas citocinas do que camundongos infectados pela cepa tipo I (RH) e pela cepa TgCatBr71. Assim, concluímos que esta cepa TgCatBr71 se assemelha bastante a cepa do tipo I (RH), tanto em relação a evolução da doença no camundongos como nos padrões da resposta imune do hospedeiro. E que apesar dessas duas cepas diferirem da cepa tipo II (ME49), resultando em graus diferentes de patologia em camundongos C57Bl/6, todas a três cepas parecem produzir semelhante resposta imune protetora do hospedeiro. / More than 2 billion people are infected with Toxoplasma gondii around the world. In the endemic region of Erechim, RS, Brazil, about 90% of the population is soropositive and about 18% of these individuals have ocular lesions with clinical manifestations. The genetic structure of strains of T. gondii has been investigated, despite the infection has spread throughout the world, the large number of intermediate hosts and the ability to reproduce sexually. Strains of T. gondii with atypical or new combination of alleles have been isolated from wild animals and other continents, such as South America and Africa, and also from patients with unusual clinical presentations. In murine models, the type I genetic lineage are highly virulent, in contrast to strains type II and type III.Our work proposes the phenotypic characterization of the host immune response against the infection by different strains of T. gondii, and the isolation and genetic strains characterization of T. gondii that infect individuals of Erechim in RS, Brazil. In the phenotypic characterization were used two strains of T. gondii already well established, the strain RH (type I) and ME49 (type II), and a strain isolated from domestic cats from Brazil, called TgCatBr71 (type BrI). Thus, by phenotyping dendritic cells of C57BL/ 6 mice infected with the strains mentioned, we observed that these strains upregulated the expression of surface molecules such as CD40, CD80, CD86 and MHC class II in DC CD11c+ although with no significant difference between the strains. With respect to the CD4+ and CD8+ cells, the observed increase in CD8+ T cells during the infection by strains RH and ME49, indicating the importance of this cell type in the protective response against T. gondii. We also evaluated the production of cytokines IL-12, IFN-g and IL-10 from spleen cells and found that mice infected by the strain type II (ME49) have increased synthesis of these cytokines than mice infected by the strain type I (RH) and the strain type BrI (TgCatBr71). Thus, we concluded that type BrI (TgCatBr71) strain is similar to type I (RH) strain, both for the evolution of the disease and also concerning the immunological parameters evaluated. Besides, despite these two strains differ from the strain type II (ME49), resulting in different degrees of pathology in mice C57BL / 6, all three strains seem to produce similar protective immune response of the host.