Tuberkuliozė (TB) – viena grėsmingiausių, plačiai pasaulyje paplitusių lėtinių infekcinių ligų, sąlygojančių didelį mirtingumą. Savalaikė jos diagnostika, tinkamas gydymas ir profilaktika lieka vieni aktualiausių medicinos uždavinių, siekiant sėkmingos TB kontrolės. Nuo 1890 metų vienintelis metodas latentinei TB infekcijai nustatyti yra įodinis tuberkulino mėginys (ITM), pasižymintis nepakankamu jautrumu, ypač BCG vakcina vakcinuotoje populiacijoje [WHO, 2004, WHO, 2006, American Thoracic Society, 2000]. Darbo tikslas - nustatyti specifinio imuninio atsako ypatumus diagnozuojant vaikų užsikrėtimą TB. Uždaviniai: 1. Įvertinti odos reakciją į tuberkuliną asmenims, kuriems įtariama TB infekcija, ir palyginti su sergančiųjų TB tyrimo duomenimis; 2. Įvertinti ir palyginti T-limfocitų išskiriamo IFN-γ kiekį asmenims, sergantiems TB ir buvusiems kontakte su sergančiuoju užkrečiama TB; 3. Palyginti in vivo ir in vitro tyrimų diagnostinę vertę, nustatant užsikrėtimą TB infekcija; 4. Įvertinti odos reakcijos į tuberkuliną dydžio ir T-limfocitų išskiriamo IFN-γ kiekio pokyčius po gydymo vaistais nuo TB; 5. Įvertinti socialinius veiksnius, galinčius įtakoti tirtų vaikų užsikrėtimą ir sirgimą TB. Tyrimas buvo atliktas Kauno medicinos universiteto Vaikų ligų klinikoje ir Romainių tuberkuliozės ligoninėje 2005–2007 m., gavus KMU Regioninio Bioetikos komiteto leidimą (leidimas atlikti biomedicinį tyrimą 2005-05-11 Nr. BE-2-32). Tirti vaikai iš Kauno regiono, jų amžius – 10-17 metų. Visi... [toliau žr. visą tekstą] / Tuberculosis (TB) is one of the oldest infectious diseases worldwide. The only method available for TB infection detection has been the tuberculin skin test (TST). Still, this tool has not proved itself as a sensitive method, especially in population previously vaccinated with BCG. The Aim of the Study: to evaluate features of specific immune response in diagnosis of TB in children. The Objectives of the Study: to assess TST in subjects who had contact with TB, and to compare with the results of patients with bacteriologically confirmed TB; to evaluate and to compare T-cell secreting IFN-γ response (T SPOT TB) in subjects with contagious TB and in subjects who had contact with TB; to compare the diagnostic value of in vivo and in vitro tests; to evaluate TST and T SPOT TB results after treatment; to assess the social factors, that may influence children to get TB. 120 subjects had been enrolled in Part I of the Study and 67 in the II. Part I. Evaluation of the immune response - 3 groups of children: “culture-confirmed TB“ group (n=23) – subjects with bacteriologically confirmed TB; “high risk for TB“ group (n=45) - subjects, who had contact with a TB-sick person; “low risk for TB“ group (n=52) – subjects with no identifiable risk for TB. Part II. children were divided into 3 groups, depending on the results of Part I of the study: Children with bacteriologically confirmed-TB (n=23); Children with latent TB infection (n=13); Healthy children (n=31). Conclusions: Positive... [to full text]

Measures of temperament have been shown to influence physiological responses. Exit velocity (EV) has been identified as an objective, robust measure of temperament that can be used to predict subsequent performance of cattle. Additionally, previous studies from our lab indicate this measure of temperament may be related to production of interferon-γ (IFN-γ), a cytokine associated with cell-mediated immunity (CMI). Whereas research has investigated effects of EV upon immune responses, the overall goal of these studies was to examine this relationship under a variety of scenarios including human handling, transportation, and exposure to endophyte-infected tall fescue (E+) for determination of its ability to influence CMI in cattle. In each of 5 experiments, calves were classified as either high or low EV animals, based upon measurements obtained prior to initiation of experimental periods. The hypothesis for these studies was that calves with high exit velocities would have lower systemic immune responses to applied treatments. Two experiments were designed to examine the relationship between exit velocity and lymphocyte IFN-γ production during and following a period of exposure to E+ seed and increased temperature humidity index conditions. Preliminary measures of this cytokine indicated a positive relationship with EV. During application of heat and E+ treatment application, no differences in IFN-γ production were detected between EV or endophyte treatment groups. However, in both experiments, after temperatures were returned to thermoneutral and E+ heifers were placed on the endophyte-free treatment, the positive relationship between exit velocity and total lymphocyte production of IFN-γ observed in baseline samples was reestablished. Similarly, during an experiment examining IFN-γ production by lymphocytes in steers during the 4 weeks following a 10h, 805 km transport study, average lymphocyte production of IFN-γ was higher and lymphocyte proportions producing IFN-γ lower in low EV steers, but total lymphocyte production of this cytokine did not differ between exit velocity treatments. In a grazing and finishing study, cattle were placed on E+ or novel endophyte pastures, with balanced representation of low and high EV treatments within each pasture. During the subsequent finishing period, blood samples for lymphocyte IFN-γ production were collected from a single high EV calf from each pasture group. Neither endophyte nor exit velocity was detected to be related with lymphocyte production of IFN-γ. In an experiment examining changes in cytokine gene expression changes during acclimation to human handling, IFN-γ, Il-6, IL-10, and IL-12 were observed to increase linearly over the experimental period in all calves, irrespective of exit velocity designation. In the same experiment, whole period pro-inflammatory tumor necrosis factor-α expression was higher for high EV calves, but interferon-γ (IFN-γ) was lower in this same treatment group. These studies, cumulatively, indicate EV may be related to systemic production of IFN-γ, but abrupt changes to an animal’s environment may serve to mask this relationship.

Submitted by ROBERTO PAULO CORREIA DE ARAÚJO (ppgorgsistem@ufba.br) on 2017-05-19T23:58:33Z No. of bitstreams: 1 TESE - Marilda - 2016 F.pdf: 1951206 bytes, checksum: f0d79f0e2b09130f482d4c5c8d7f00d3 (MD5) / Made available in DSpace on 2017-05-19T23:58:34Z (GMT). No. of bitstreams: 1 TESE - Marilda - 2016 F.pdf: 1951206 bytes, checksum: f0d79f0e2b09130f482d4c5c8d7f00d3 (MD5) / Introdução: A avaliação de risco para tuberculose (TB) em profissionais da saúde baseia-se no número de indivíduos doentes atendidos nas instituições, na evidência de sua transmissão entre pessoas dentro das instituições, ou cálculo de taxas de conversão do teste cutâneo tuberculínico (TCT). Sugere-se que os resultados negativos para este teste sejam repetidos periodicamente, de acordo com o risco que a instituição apresente e, ou, após exposições ocupacionais. O fato de apenas 10% das pessoas infectadas com Mγcobacterium tuberculosis desenvolverem a doença clínica sugere que diversos mecanismos podem desempenhar um papel importante na imunopatogênese da doença. Estudos genéticos estão sendo desenvolvidos com o objetivo de identificar possíveis marcadores de predisposição ou proteção ao desenvolvimento desta doença e sugerem que o desequilíbrio na produção de citocinas pró e anti-inflamatórias tem um importante papel na TB. Objetivo: Avaliar a liberação de interferon gama (IFN-γ) e o polimorfismo de citocinas nos PS com TCT de repetição, negativo e positivo, que trabalham em uma unidade de referência secundária e terciária em TB. Métodos: A população do estudo foi constituída por 48 profissionais TCT de repetição negativo, com resultado < 5 mm e 45 TCT positivo > 10 mm. O DNA genômico foi extraído a partir de sangue total, utilizando o kit de extração de DNA mini spin Kasvi. Foi realizada a genotipagem das citocinas (IL6, IL10, TNF, IFN-γ, TGFB1) e a associação entre o polimorfismo +874T/A do geneIFN- γ ,o resultado do ensaio de liberação de interferon gama IGRA (QFT®) e o TCT. Resultados: Não foi observada diferença estatística no polimorfismo do gene IFN-γ +874 T/A e o resultado do IGRA e TCT. A concordância entre o TCT e IGRA foi feita utilizando o índice Kappa que mostrou κ=0,24. Os resultados relativos aos fenótipos previstos de alto (TT), intermediário (TA) e baixo produtor (AA) de IFN-γ, a partir do polimorfismo na posição +874T/A, em ambos os grupos mostrou que a maior frequência foi o de baixo produtor. Ao analisar o grupo TCT+ / IGRA +, os dados mostram correlação dos testes in vivo e in vitro para reatividade em 24 indivíduos. O polimorfismo desses indivíduos tem o perfil dos fenótipos previstos de baixo produtor, sendo apenas 6 de intermediário e 3 de alto produtor. Conclusão: A concordância entre o TCT e o IGRA na população estudada é mediana e não foi observada diferença no polimorfismo do gene IFN-γ+874T/A para frequência de fenótipo previsto de baixo produtor, comparando os grupos do estudo e seus respectivos IGRA. Os polimorfismos dos genes IFN γ +874T/A, TNF -308G/A, IL6 -174G/C IL10 - 1082G/A, -819C/T e -592C/A e TGFβ1 -509 C/T não parecem ser marcadores de predisposição ou proteção ao desenvolvimento da TBIL. Foi encontrada diferença estatística no gene TGF1 +869 T/C.

Submitted by Hiolanda Rêgo (hiolandar@gmail.com) on 2013-04-24T19:07:37Z No. of bitstreams: 1 Dissertação_Med_ Tatiana Moura.pdf: 1314903 bytes, checksum: d553217eb6f2d6d979a75a8179ee209b (MD5) / Approved for entry into archive by Flávia Ferreira(flaviaccf@yahoo.com.br) on 2013-04-26T16:49:27Z (GMT) No. of bitstreams: 1 Dissertação_Med_ Tatiana Moura.pdf: 1314903 bytes, checksum: d553217eb6f2d6d979a75a8179ee209b (MD5) / Made available in DSpace on 2013-04-26T16:49:27Z (GMT). No. of bitstreams: 1 Dissertação_Med_ Tatiana Moura.pdf: 1314903 bytes, checksum: d553217eb6f2d6d979a75a8179ee209b (MD5) / A Leishmaniose Tegumentar Americana (LTA) é uma doença endêmica no Brasil. No entanto, não existe um bom modelo experimental para o estudo da doença. Nosso objetivo foi desenvolver um modelo de infecção com L. braziliensis, o principal agente etiológico da LTA em nosso país, levando em consideração o inoculo de parasitas e o sítio de infecção. [MATERIAL E MÉTODOS] Camundongos BALB/c foram infectados com 105 Leishmania braziliensis (MHOM/BR/01/BA788), na derme da orelha. Os animais foram acompanhados durante 10 semanas para a avaliação do desenvolvimento da lesão e para a avaliação da resposta imune. [RESULTADOS] Observamos que a expansão parasitária foi acompanhada pelo desenvolvimento de uma lesão na derme da orelha, similar à observada em pacientes com LTA (lesão nodular e ulcerada no centro), a qual regrediu espontaneamente, como evidenciado pela presença de uma cicatriz. A análise histopatológica da orelha infectada mostrou a presença de, inicialmente, um infiltrado focal constituído por células mononucleares (linfócitos e monócitos), neutrófilos e poucos parasitas. No auge do desenvolvimento da lesão, havia predominância de macrófagos infectados os quais foram, em seguida, substituídos por um infiltrado inflamatório constituído por histiócitos, plasmócitos, neutrófilos e fibroblastos e pela ausência de parasitas. Os parasitas podem ser detectados no linfonodo regional, durante toda a infecção. A análise da expressão de quimiocinas no linfonodo regional mostra um aumento na expressão de quimiocinas recrutadoras de monócitos/macrófagos e neutrófilos Observamos também um aumento na expressão de IFN-γ, IL-4, IL-5 e IL-10, tanto por células T CD4+ quanto por células T CD8+. Com a regressão da lesão, a expressão destas citocinas diminuiu. [CONCLUSÃO] A inoculação de L. braziliensis na derme da orelha de camundongos constitui um modelo de resistência devido ao desenvolvimento de uma resposta imune do tipo Th1. Contudo, nesse modelo, os parasitas são capazes de sobreviver no linfonodo regional de camundongos infectados apesar do desenvolvimento de uma resposta imune capaz de curar a lesão / Salvador

Background: Diminished cytokine production in infancy has been associated with an increased risk for allergen sensitization and early-life wheeze. Objective: We sought to assess the effect of low cytokine production in the first year of life on the development of wheeze through age 13 years. Methods: Cytokine production (IFN-γ and IL-2) by mitogen-stimulated mononuclear cells was determined from peripheral blood samples (9.4 months, n = 118) in a subset of healthy infants enrolled in the Tucson Children's Respiratory Study. The occurrence of wheeze during the previous year was ascertained at ages 2, 3, 6, 8, 11, and 13 years by means of questionnaire. Relative risk for wheeze was computed with generalized estimating equations. Results: The risk of wheezing between 2 and 13 years was significantly higher for subjects with low 9-month IFN-γ production (relative risk, 2.29; 95% CI, 1.35-3.89) and borderline significant for those with intermediate IFN-γ production (relative risk, 1.59; 95% CI, 0.95-2.68) compared with those who produced high levels of IFN-γ (P value for linear association = .002). Nine-month IL-2 production was unrelated to wheeze. In relation to complex wheezing phenotypes, 9-month IFN-γ production was inversely related to toddler wheeze (occurring only before age 6 years, P = .03) and chronic wheeze (occurring before and after age 6 years, P = .007) but not school-age wheeze (occurring only after age 6 years, P = .06). Conclusion: The results suggest that characteristics of the immune system present during the first year of life can anticipate the likelihood of development of episodes of airway obstruction characterized by wheezing. Clinical implications: Immune susceptibility to asthma is established very early during postnatal life.

Au cours de cette étude, nous avons approfondi nos connaissances concernant l’effet des conditions de culture sur la quantité et la qualité d’une protéine recombinante produite par des cellules CHO. En particulier, nous avons étudié l’influence de 3 composés (citrate de fer, pluronic F-68 et éthanolamine) présents dans le milieu BDM mais absent du milieu RPMI avec sérum (FCS-RPMI) sur la croissance des cellules CHO, la production de l’interféron-gamma humain recombinant (IFN-γ) ainsi que sa qualité. L’ajout de pluronic F-68 (0,1%) et de citrate de fer (500 µM) dans le milieu RPMI sans sérum a permis d’obtenir une croissance cellulaire comparable à celle obtenue avec le milieu FCS-RPMI. Par ailleurs, dans ces conditions de culture, la production de l’IFN-g est également augmentée. L’ajout de citrate de fer dans le milieu FCS-RPMI permet non seulement d’améliorer la croissance des cellules CHO mais également la production de l’IFN-γ. Avec le milieu FCS-RPMI, la macrohétérogénéité de la glycosylation de l’IFN-γ change au cours du procédé discontinu, cette dernière est maintenue constante uniquement lorsque du citrate de fer est ajouté à ce même milieu de culture. En outre, des activités gélatinase et caséinase appartenant aux familles des métalloprotéases et des protéases à sérine ont été mises en évidence au cours des cultures de cellules CHO. Quel que soit le milieu utilisé (RPMI, BDM avec ou sans sérum), l’ajout de citrate de fer permet de maîtriser et d’éviter la protéolyse de l’IFN-γ. Enfin, la relation entre le degré de glycosylation macroscopique de l’IFN- γ et son activité biologique (immunomodulatrice) in-vitro a été établie / In this study, we characterized the effect of culture conditions on the quantity and the quality of a recombinant protein, IFN-γ, produced by CHO cells. In particular, we studied the effect of 3 components (iron citrate, pluronic F-68 and ethanolamine) that are present in the BDM medium, but completely lacking in RPMI serum medium (FCS-RPMI) on CHO cell growth, as well as the production and quality of recombinant IFN-γ.The addition of Pluronic F-68 (0.1%) and iron citrate (500 µM) in RPMI without serum resulted in growth kinetic performances similar to those observed in FCS-RPMI. Furthermore, in these culture conditions, IFN- γ production was improved. Addition of iron citrate in FCS-RPMI improved cell growth, as well as IFN-γ production. Whereas the glycosylation pattern of recombinant IFN-γ produced by CHO cells was not constant when the culture was performed in FCS-RPMI, the glycosylation pattern of IFN-γ remained constant when iron citrate was added in the medium. In addition, gelatinase and caseinase enzymatic activities in CHO batch cultures were detected, due most likely to enzymes of the metalloproteases and serine protease families. Despite the type of medium used (RPMI, BDM with or without serum), addition of iron citrate minimized IFN-g proteolysis. Finally, the relationship between the macroglycosylation pattern of IFN-g and its in-vitro biological (immunomodulatory) activity was demonstrated

No description available.

L’activation des cellules NKCD56dim par l’engagement ou non du récepteur FγRIIIA/CD16A entraîne la perte d’expression membranaire de celui-ci par un mécanisme dépendant au moins en partie de la metalloprotéase ADAM17. Celle-ci clive le récepteur entre l’Alanine 195 et la Valine 196 et agit exclusivement en cis. La modulation d’expression du FγRIIIA/CD16A est un marqueur d’activation des cellules NK plus fortement corrélé à la dégranulation qu’à la production d’IFN-γ. L’engagement du récepteur FγRIIIA/CD16A ou le co-engagement des récepteurs activateurs des NKCD56dim induisent de manière non corrélée la dégranulation et la production d’IFN-γ. Cette dichotomie fonctionnelle varie selon les donneurs et dépend de l’expression des récepteurs inhibiteurs spécifiques des molécules du CMH-I. La production d’IFN-γ est ainsi associée à l’expression des KIRs (Killer like-Immunoglobuline Receptor) mais pas à celle du NKG2A. Une meilleure compréhension des réponses effectrices dépendantes du FγRIIIA/CD16A est importante pour améliorer l’efficacité thérapeutique des anticorps monoclonaux à visée anti-tumorale. / FγRIIIA/CD16A-dependent or independent activation of CD56dim NK cells induces down-modulation of this receptor. The mechanism partially involves the ADAM17 metalloprotease, which cleaves the FγRIIIA/CD16A between Alanine 195 and Valine 196 and acts exclusively in cis. FγRIIIA/CD16A downmodulation is a marker of NK cell activation more strongly correlated with degranulation than to IFN-γ- production. FγRIIIA/CD16A engagement or activating receptors co-engagement on CD56dim NK cell induces degranulation and IFN-γ-production, which are not correlated. This functional dichotomy depends on the donor and on the CMH-I-specific inhibitory receptor expression. IFN-γ-production is thus associated with KIRs (Killer like-Immunoglobuline Receptor) but not with NKG2A expression. Understanding the FγRIIIA/CD16Adependent functional responses is essential to improve the efficacy of monoclonal antibodies used in cancer therapy.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-02-03T13:11:46Z No. of bitstreams: 1 caiocesardesouzaalves.pdf: 1872262 bytes, checksum: f03fadd9407262d508f6744a7f73820f (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-02-03T13:14:01Z (GMT) No. of bitstreams: 1 caiocesardesouzaalves.pdf: 1872262 bytes, checksum: f03fadd9407262d508f6744a7f73820f (MD5) / Made available in DSpace on 2017-02-03T13:14:01Z (GMT). No. of bitstreams: 1 caiocesardesouzaalves.pdf: 1872262 bytes, checksum: f03fadd9407262d508f6744a7f73820f (MD5) Previous issue date: 2007-08-30 / A Paracoccidioidomicose é uma micose sistêmica humana causada pelo fungo dimórfico, Paracoccidioides brasiliensis, que acomete, principalmente, indivíduos adultos do sexo masculino. O presente estudo propôs a padronização do modelo de infecção com P. brasiliensis pela via intratorácica em camundongos BALB/c. Este estudo foi monitorado pela detecção do P. brasiliensis através da contagem de unidades formadoras de colônia e pela presença de DNA do fungo nos pulmões dos animais infectados em diferentes pontos pósinfecção (2o, 7o, 15o, 30o, 45o, 60o e 90o dias) e a taxa de sobrevida dos camundongos. Além disto, foram avaliados alguns parâmetros imunológicos como a produção de óxido nítrico, TNF-alpha, IFN-gama, e IL-10 por células presentes no lavado intratorácico, contagem total e diferencial do número de células do lavado intratorácico, o estudo histopatológico dos pulmões e a detecção de anticorpos específicos anti-P. brasiliensis nos pulmões e no soro. Os resultados mostram um aumento gradual do número de colônias e de DNA de P. brasiliensis nos pulmões. Até o 15o dia após a infecção pode ser observado um aumento na produção de óxido nítrico e IFN-gama pelas células do lavado intratorácico, bem como um aumento do número total de células e da porcentagem de leucócitos mononucleares. A partir do 30o dia após a infecção observa-se um aumento de anticorpos específicos (IgG1) no soro e no pulmão, um aumento da produção de IL-10 e TNF-alpha pelas células do lavado intratorácico e conseqüente diminuição da produção de IFN-gama e óxido nítrico. Além disso, observa-se um aumento da porcentagem de células polimorfonucleares no lavado. No estudo histopatológico pode ser constatado um aumento gradual no tamanho e complexidade dos granulomas presentes nos cortes histológicos. Os camundongos utilizados no estudo de sobrevida começaram a morrer no 60o dia após a infecção. Os resultados mostram uma resposta inicial do hospedeiro com um perfil Th1 mudando durante a infecção para uma resposta Th2 que leva ao óbito dos camundongos BALB/c. / Paracoccidioidomycosis or South American blastomycosis, is a chronic granulomatous human male infection caused by the Paracoccidioides brasiliensis. The present study it considered the standardization of the model of infection with P. brasiliensis for the intrathoracic route in BALB/c mice. This study was monitored by the detection of the P. brasiliensis through the counting of colony forming units and by the presence of DNA of fungi in the lungs of the infected animals in different points (2, 7, 15, 30, 45, 60 and 90 days) and the survival rate of the mice. Moreover, some immune parameters had been evaluated as the nitric oxide production, TNF-alpha, IFN-gamma, and IL-10 for cells in the intrathoracic washed, total and distinguishing counting of cells of the intrathoracic washed, the lung histopathology and the detection of specific antibodies anti-P. brasiliensis in the lungs and serum. The results show a gradual increase of the number of colonies and P. brasiliensis DNA in the lungs. Until 15 day after the infection can be observed an increase in the nitric oxide production and IFN-gamma for the cells of the washed, as well as an increase of the total number of cells and the percentage of mononuclear. From 30 day after the infection observes an increase of specific antibodies (IgG1) in the serum and the lung, an increase of the production of IL-10 and TNF-alpha for the cells of the washed and consequent reduction of the IFN-gamma production and nitric oxide. Moreover, observed an increase of the percentage of cells polimorphonuclear in the washed. In the histopathology it can be evidenced a gradual increase in the size and complexity of granulomas in the cuts. The mice used in the survival study had started to die in 60 day after the infection. The results show an initial reply of the host with a Th1 profile moving during the infection for a Th2 reply that leads to the death of the BALB/c mice.

Toxoplasma gondii ist ein weltweit verbreiteter Parasit. In Europa ernährt sich der Endwirt (Katzen) hauptsächlich von kleinen Säugetieren wie Myodes glareolus und Microtus spp. (Wühlmäusen) und Apodemus spp., seltener von Mus spp. Erstere zeigen gegenüber Mus spp. erhöhte Prävalenzen von T. gondii und überleben diese eher als Mus spp. Daher wird vermutet, dass Wühlmäusen und Apodemus spp. eine größere Rolle als Zwischenwirte besitzen, als Mus spp. Der Schutz wird auf das IFN-γ-induzierte IRGb2-b1 zurückgeführt, die den zentralen parasitären Virulenzfaktor ROP5 inhibiert. Daher liegt der Fokus meiner Arbeit auf der protektiven Rolle von IRGb2-b1 bei der Infektion mit T. gondii in Wühlmäusen und Apodemus spp. Mit dieser Arbeit trage ich nützliche Werkzeuge zur Erforschung von Wühlmäusen bei, wie ein rekombinantes M. glareolus IFN-γ Zytokin und neuartige Zellsysteme. Alle untersuchten Wühlmaus-Systeme besaßen einen Phänotyp bei Infektion mit in vivo Resistenz beschrieben wurde: einem IFN-γ-vermittelten Reduktion der Parasitenbürde (mit Wirtszelltod für Typ I Parasiten, ohne für Typ II). Darüber hinaus bestätigen vorläufige Resultate aus Wühlmäusen und Apodemus spp. in Deutschland hohe genetische Vielfalt der IRGb2 Untereinheit zeigen, insbesondere an der vermuteten Grenzfläche zum ROP5, was auf eine Rolle dieses Proteins bei der Infektion hindeutet. Um die Funktion der IRGb2-b1 Proteine zu untersuchen, habe ich ein Zellkultur System, entwickelt, welches erlaubt wild-derived Gene stabil zu exprimieren. Dieses Setup gestattet es, die Auswirkungen von Polymorphismen in Irg Genen bei der Infektion mit T. gondii zu evaluieren. Insgesamt habe ich Werkzeuge erarbeitet, um den Ansatz der Öko-Immunologie in eine Labor-Umwelt zu bringen, wodurch die molekulare Untersuchung ökologisch relevanter Arten möglich wird. Durch Anwendung dieser Werkzeuge stütze ich die Hypothese, dass nicht-Mus Nagetiere, insbesondere M. glareolus, ein bedeutendes Reservoir für T. gondii darstellen. / Toxoplasma gondii is an ubiquitous parasite grouped in three main clonal lineages, type I-III. In Europe, felids, definitive hosts for the parasite, mostly prey on small mammals of Myodes glareolus and Microtus spp. (voles), and Apodemus spp., rather than Mus spp. Voles and Apodemus spp. also display higher T. gondii prevalence and survive infection to a larger extent than Mus spp., although tolerant Mus subspecies exist. This suggests that voles and Apodemus spp. are more relevant intermediate hosts than Mus spp.. Resistance to infection relies on the IFN-γ-induced IRGb2-b1, which inhibits the major parasite virulence factor ROP5. Thus, this work focuses on the protective role of IRGb2-b1 during T. gondii infection in voles and Apodemus spp. With this project I contribute with valuable tools for research on voles, such as the supply of the recombinant M. glareolus IFN-γ cytokine and novel cell systems. All vole systems show a phenotype to type I infection which is associated with in vivo resistance in Mus spp: IFN-γ-mediated host cell death and a decrease in parasite burden. The latter without cell death was observed for type II parasites, suggesting novel protective mechanisms. Further, preliminary results from voles and Apodemus spp. in Germany confirm the expected high diversity in the IRGb2-like subunit, especially at the putative interface with ROP5, which suggests a role of the protein during infection. To assess the role of IRGb2-b1-like in this phenotype, I developed a system which allows establishment of cell lines stably expressing wild-derived Irg-like genes. This setup allows evaluation of the effect of polymorphisms of Irg-like genes during infection. Taken together, I have provided tools to bring eco-immunology into a lab setting to perform molecular investigations of ecologically relevant species. Using these tools, I offer support for the hypothesis that non-Mus rodents, especially M. glareolus, constitutes a relevant T. gondii reservoir in Germany.