A candidíase vulvovaginal corresponde a uma das mais frequentes infecções do trato reprodutivo. Estima-se que 75% das mulheres na idade reprodutiva experimentarão pelo menos um episódio de candidíase vulvovaginal durante suas vidas, a maioria evoluirá com episódios infrequentes, entretanto, 5% sofrerão recorrência, ou seja, quatro ou mais episódios de candidíase vulvovaginal comprovadas clínica e laboratorialmente no período de 1ano. Os mecanismos pelos quais as recorrências ocorrem ainda são pouco conhecidos, estando provavelmente relacionados à alterações na imunidade local. O presente estudo teve como objetivo avaliar as associações entre os polimorfismos nos genes que codificam a lecitina ligadora de manose (MBL) e do antagonista do receptor da interleucina 1 (IL1-Ra) com a candidíase vulvovaginal recorrente (CVVR) em mulheres brasileiras. Foram estudadas 100 mulheres portadoras de CVVR atendidas no Serviço de Imunologia Genética e Infecções do Trato Reprodutivo da Disciplina de Ginecologia da Faculdade de Medicina da Universidade de São Paulo. Para a análise dos polimorfismos nos genes que codificam para a MBL e o IL1-Ra realizou-se coleta de células bucais que foram enviadas para Division of Immunology and Infectious Diseases of Weill Medical College of Cornell University Resultados: Mulheres com candidíase vulvovaginal recorrente apresentaram maior frequência de polimorfismo no códon 54 do gene que codifica a MBL quando comparadas a mulheres saudáveis. Não foram observadas diferenças estatisticamente significativas na frequência do polimorfismo do gene que codifica o IL1-Ra entre os grupos estudados / Vulvovaginal candidiasis is the most common genital infection in women during their childbearing years. About 75% of women suffer at least one syntomatic episode during their lives. Most of them will have infrequent episodes, but 5% will suffer recurrent episode of vulvovaginal candidiasis. The mechanisms responsible for recurrent vulvovaginal candidiasis (RVCC) remain a matter of speculation, although an alteration in local immunity appears to be a major factor. The aim of this study was to assess the correlation between polymorphisms in the genes coding for mannose-binding lectin (MBL) and interleukin-1 receptor antagonist (IL1-Ra) and RVCC in women from São Paulo, Brazil. The study population consisted of 100 women with RVCC, who were seen at Serviço de Infecções do Trato Reprodutivo da Disciplina de Ginecologia da Faculdade de Medicina da Universidade de São Paulo. To analyse for the MBL códon 54 gene polymorphism and for IL1-Ra, buccal cells were obtained with a cotton swabs and shipped to New York at ambient temperature. The polymorphisms were identified in the Division of Immunology and Infectious Diseases of Weill Medical College of Cornell University. Results: Women with RVVC present a high frequency of polymorphisms at codon 54 in the gene coding for MBL; on the other hand there were no differences in polymorphism frequency in the gene coding for IL1-Ra when compared to control women

Malária é uma das principais causas de doença e morte no mundo, principalmente de crianças. É considerada a força de seleção evolucionária mais forte que se conhece na história recente do genoma humano. Além dos fatores ambientais e do próprio parasito, fatores genéticos do hospedeiro têm um papel fundamental tanto na suscetibilidade como na evolução clínica da infecção. O sistema imune inato reconhece os plasmódios através de um número limitado de receptores de reconhecimento padrão (PRRs) e inicia vários mecanismos de defesa que resultam no desenvolvimento de inflamação e resistência do hospedeiro à infecção. Mas, a eliminação completa do parasito requer respostas imunes adaptativas que são amplificadas pela ativação do sistema imune inato. As manifestações clínicas de malária são dependentes dos níveis de citocinas próinflamatórias circulantes produzidas, as quais em níveis altos contribuem para a imunopatologia da doença. O balanço entre respostas pró e antiinflamatórias dirigidas contra o parasito é considerado crítico para a proteção clínica, assim a resposta imune inata pode contribuir tanto para proteção da malária como para modular a resposta imune adaptativa. Neste estudo, nós investigamos polimorfismos de um único nucleotídeo (SNP) dos genes de três PRRs: TLR, MBL e CR1 de indivíduos infectados por Plasmodium e residentes em áreas endêmicas de malária no Brasil. Os SNPs TLR1 (I602S), TLR4 (D229G), TLR6 (S249P), TLR9 (T-1237C/ -1486C), MBL [exon 1 nos códons 52, 54, e 57 (MBL2*A ou D, A ou B e A ou C, respectivamente); na região do promotor na posição -221 (*X ou *Y); e na posição +4 da região não traduzida (*P ou *Q)] e CR-1(C5507G) foram determinados por PCR-RFLP. Nós observamos associações entre os polimorfismos TLR1 I602S, TLR6 S249P e da região não traduzida +4 (*Q) e manifestações clínicas de malária e entre os polimorfismos TLR9 T-1486C, TLR T-1237C, MBL*D (códon 52) e do diplótipo de produção insuficiente de MBL (XA+O/O) e parasitemias mais altas. Nenhuma associação foi observada entre o polimorfismo CR-1 C5507G e manifestações clínicas de malária ou com parasitemia. Ao analisarmos juntos os polimorfismos de MBL e TLR, observamos que indivíduos com diplótipo de produção suficiente de MBL (YA/YA+YA/XA+YA/O+XA/XA) TLR1 I602S tinham menos manifestações clínicas de malária e indivíduos com diplótipo de produção suficiente de MBL e não carreadores do alelo TLR9 -1486C tinham parasitemias mais baixas do que os indivíduos com diplótipo de produção insuficiente de MBL e carreadores dos alelos variantes de TLR1 I602S e TLR9 -1486C, respectivamente. Juntos, nossos dados indicam que polimorfismos do promotor de TLR-9 e os diplótipos de produção insuficiente de MBL (XA+O/O) devem de algum modo controlar o nível de parasitemia por plasmódios enquanto a deficiência de TLR1 parece predispor para a presença de manifestações clínicas de malária. Também, podemos sugerir que existe uma cooperação entre TLR1, TLR9 e MBL na ativação da resposta imune inata na malária. Estes achados genéticos devem contribuir para o entendimento da patogênese da malária e levantar uma questão potencialmente interessante que é digna de investigações posteriores em outras populações a fim de validar a contribuição genética destes loci na patogênese da malária / Malaria is one of the major causes of disease and death worldwide, mainly of children. It is also the strongest known force for evolutionary selection in the recent history of the human genome. Besides environmental and parasite factors, host genetic factors play a major role in determining both susceptibility to malaria and the course of infection. Innate immune mechanisms directed against Plasmodium parasites both contribute to protection from malaria and modulate adaptive immune responses. The innate immune system recognizes Plasmodium via a limited number of pattern-recognition receptors (PRRs) and initiates a broad spectrum of defense mechanisms that result in the development of inflammation and host resistance to infection. But, the complete control of the infection requires adaptive immune responses; and the innate immune system is also very efficient in instructing the cellular mediators of adaptive immunity to lead a powerful additional strike force against the parasite. Clinical malaria is characterized by high levels of circulating proinflammatory cytokines, which are thought to contribute to the immunopathology of the disease. The balance between pro- and anti-inflammatory responses toward the parasite is considered critical for clinical protection. The innate immune system initiates and thus sets the threshold of immune responses. In this study, we investigated single nucleotide polymorphisms (SNP) in the genes of three PRRs: TLR, MBL and CR1 in Plasmodium-infected individuals living in endemic areas of Brazil. The SNPs TLR1 (I602S), TLR4 (D229G), TLR6 (S249P), TLR9 (T-1237C/ -1486C), MBL [in the coding sequence of exon 1 at codons 52, 54, and 57 (MBL2*A or D, A or B, and A or C, respectively); in the promoter region at position -221 (*X or *Y); and in the untranslated sequence at position +4 (*P or *Q)] and CR-1(C5507G) were determined by PCR-RFLP. We observed associations of the TLR1 I602S, TLR6 S249P and untranslated sequence at position +4 MBL (*Q) variants with clinical manifestations of malaria and of the TLR9 T-1486C, TLR9 T-1237C, MBL2*D and MBL-insufficient diplotype (XA+O/O) with higher parasitemias. No association was observed to the CR-1 C5507G ) and clinical manifestations of malaria or parasitemia. Also, we observed that individuals with MBLsufficient haplotype (YA/YA+YA/XA+YA/O+XA/XA) and not bearing the allele TLR1 I602S had less clinical manifestations of malaria and individuals with MBL-sufficient haplotype and not bearing TLR9 -1486C had lower parasitemias when compared to individuals with MBL-insufficient diplotype and bearing the variant alleles TLR1 I602S and TLR9 -1486C, respectively. Altogether, our data indicate that TLR-9 promoter and MBL-insufficient haplotype (XA+O/O) polymorphisms to some extent may control the level of Plasmodium parasitemia while TLR1 deficiency seems to predispose to mild malaria. Also, they could suggest cooperation among TLR1, TLR9 and MBL in the immune response against malaria. These genetic findings may contribute to the understanding of the pathogenesis of malaria and raise a potentially interesting issue that is worthy of further investigation in other population in order to validate the genetics contribution of these loci to the pathogenesis of malaria

The thesis is divided in to five chapters. Chapter I: Synthesis of New thiolevomannosan derivatives In this chapter, a general and efficient method for the synthesis of conformationally locked thiosugars has been discussed. An unprecedented synthesis of a novel thioorthoester and its synthetic utility in glycosylation has been demonstrated. Chapter II: Studies on -Mannosidase Inhibitors The synthesis and evaluation of novel, conformationally locked glycomimic, thiolevomannosan and its analogs sulfoxide and sulfone starting from readily available D-mannose is discussed in this chapter. This is the first report of thiosugar derivatives with enhanced potency compared to kifunensine. Docking and biochemical studies have been discussed. Chapter III: Studies on Novel Cyclic Tetraselenides of Mannose In this chapter, the syntheses and structural properties of novel cyclic tetraselenides starting from mannose have been discussed. These tetraselenides are the first of their kind where all four selenium atoms are arranged in a cyclic manner as the backbone of mannose. X-ray structures have been reported for the tetraselenides. Chapter IV: Novel Chalcogenides of Uridine and Thymidine: Synthesis and Applications An efficient and simple method to synthesise disulfides and diselenides of thymidine and uridine derivatives has been demonstrated in this chapter. The utility of these disulfides in various ring opening reactions as well in Michael addition reactions has been demonstrated. Chapter V: Studies on New, Potent Urease Inhibitors In this chapter, a facile one-pot synthesis of thio and selenourea derivatives under mild conditions by the reaction of amines and commercially available Viehe’s iminium salt in the presence of benzyltriethylammonium tetrathiomolybdate as sulfur transfer reagent and tetraethylammonium tetraselenotungstate as selenium transfer reagent has been discussed. A few of the urea derivatives have shown potent inhibitor activity in the nanomolar range for jackbean urease.

Cystic fibrosis (CF) is a single gene Mendelian disorder characterized by pulmonary disease and pancreatic insufficiency. Pulmonary disease is the major cause of death in CF patients. Although some cystic fibrosis transmembrane conductance regulator (CFTR) genotypes are associated with less severe disease, patients possessing the same genotype show great variation in pulmonary disease severity and progression. Genes involved in modulating the inflammatory response and genes increasing susceptibility to infection are proposed as modifiers of pulmonary disease severity. Polymorphisms selected for based on evidence that they affect the function of the gene and prevalence of the putative risk allele: 1) antiprotease gene alpha-1-antitrypsin (alpha-1-AT), 2) innate immunity genes: mannose binding lectin (MBL2) (promoter [G→C] at -221 and codon 52 (Arg52Cys, D allele), 54 (Gly54Asp, B allele), and 57 (Gly57Glu, C allele), and pulmonary surfactant genes SPA-1 (Arg219Trp), SPA-2 (Thr9Asn, Lys223Gln) and SPD (Thr11Met), 3) antioxidant genes GSTM1 and T1 (gene deletion polymorphisms), GSTP1 (Ile105Val) and GCLC repeats, 4) mucin genes (MUC2 and MUC5B). Pulmonary disease progression and survival in patients with chronic Burkholderia cepacia complex (BCC) infection were also investigated controlling for genomovar and RAPD type of the organism. BCC infection was associated with more severe pulmonary disease progression and worse survival. Alpha-1-AT genotype was not a major contributor to variability of pulmonary disease severity, but the results suggest that alpha-1-AT plasma levels during pulmonary infections may be affected by poor nutritional status. We showed similar pulmonary disease progression and MBL2 genotype. Contrary to the previous literature, wild-type MBL2 genotype was associated with steeper decline in pulmonary disease over time following chronic infection with BCC, but genotype was not associated with increased susceptibility to BCC infection. We showed inconsistant results for the pulmonary surfactant gene polymorphisms, GSTM1, T1 and GSTP1 polymorphisms, and number of repeats for GCLC and MUC5B depending on the phenotype investigated. We conclude that some of the variability in pulmonary disease severity and progression in CF is explained by polymorphisms in secondary genes.

Cystic fibrosis (CF) is a single gene Mendelian disorder characterized by pulmonary disease and pancreatic insufficiency. Pulmonary disease is the major cause of death in CF patients. Although some cystic fibrosis transmembrane conductance regulator (CFTR) genotypes are associated with less severe disease, patients possessing the same genotype show great variation in pulmonary disease severity and progression. Genes involved in modulating the inflammatory response and genes increasing susceptibility to infection are proposed as modifiers of pulmonary disease severity. Polymorphisms selected for based on evidence that they affect the function of the gene and prevalence of the putative risk allele: 1) antiprotease gene alpha-1-antitrypsin (alpha-1-AT), 2) innate immunity genes: mannose binding lectin (MBL2) (promoter [G→C] at -221 and codon 52 (Arg52Cys, D allele), 54 (Gly54Asp, B allele), and 57 (Gly57Glu, C allele), and pulmonary surfactant genes SPA-1 (Arg219Trp), SPA-2 (Thr9Asn, Lys223Gln) and SPD (Thr11Met), 3) antioxidant genes GSTM1 and T1 (gene deletion polymorphisms), GSTP1 (Ile105Val) and GCLC repeats, 4) mucin genes (MUC2 and MUC5B). Pulmonary disease progression and survival in patients with chronic Burkholderia cepacia complex (BCC) infection were also investigated controlling for genomovar and RAPD type of the organism. BCC infection was associated with more severe pulmonary disease progression and worse survival. Alpha-1-AT genotype was not a major contributor to variability of pulmonary disease severity, but the results suggest that alpha-1-AT plasma levels during pulmonary infections may be affected by poor nutritional status. We showed similar pulmonary disease progression and MBL2 genotype. Contrary to the previous literature, wild-type MBL2 genotype was associated with steeper decline in pulmonary disease over time following chronic infection with BCC, but genotype was not associated with increased susceptibility to BCC infection. We showed inconsistant results for the pulmonary surfactant gene polymorphisms, GSTM1, T1 and GSTP1 polymorphisms, and number of repeats for GCLC and MUC5B depending on the phenotype investigated. We conclude that some of the variability in pulmonary disease severity and progression in CF is explained by polymorphisms in secondary genes.

Tuberculosis is one of the most prevalent infectious diseases globally due to the successful survival mechanisms displayed by Mycobacterium tuberculosis (Mtb). Mtb primarily infects alveolar macrophages (AMs) and is able to live intracellularly for extended periods of time due to a number of virulence factors which inhibit the antibacterial mechanisms of the AMs. This aspect of the Mtb life cycle means TB treatments suffer from poor bioavailability and efficacy. Additionally, the rise in resistant strains of Mtb means the use of higher doses and the use of alternative second and third line drugs which increase the risk of systemic toxicity. Drug encapsulation is a novel approach that can provide more favourable drug pharmacokinetics and pharmacodynamics. The aim of this project was to develop a liposomal drug delivery system to target Mtb infected alveolar macrophages. The system involved the encapsulation of two drugs; the antibiotic gatifloxacin (GFLX) and Mtb virulence factor inhibitor CV7. The hypothesis was that the two different antibacterial mechanisms would work in synergy and increase the efficacy of the treatment. AM targeting and receptor-mediated endocytic uptake was encouraged by the presence of a ligand attached to the surface of the liposome. Furthermore a pH-sensitive release mechanism was to be incorporated into the liposome to encourage the release of the encapsulated drugs in the vicinity of the intracellular bacteria. The intention was to produce a drug delivery system to enable a TB therapy regime of fewer, lower doses to increase compliance and reduce systemic toxicity by increasing efficacy through improved bioavailability. GFLX was successfully encapsulated using a weak base active loading method. To establish encapsulation efficiency, a homogeneous fluorescence assay able to quantify intra- and extra-liposomal gatifloxacin simultaneously was developed. pH-sensitive release of the payload could be achieved using a pH-sensitive peptide with a novel design based on chimeric structure, namely P3. CV7 was successfully encapsulated using a weak acid active loading method. CV7 liposomes were able to be functionalised by the incorporation of a mannose ligand on the surface of the liposome. An inhibition assay using the target enzyme of CV7, MptpB, was optimised to assess efficacy of liposomally encapsulated and released CV7. Flow cytometry and confocal microscopy studies confirmed that the liposomal formulations were internalised by the target macrophage cell line, J774a.1. Mannose liposomes conveyed superior uptake kinetics. Further confocal microscopy showed that after internalisation the liposomes entered the endolysosomal pathway and colocalised with BCG. A BCG-macrophage infection model was used to determine the intracellular efficacy of the liposomal formulations. Encapsulated CV7 displayed increased efficacy over free CV7, while encapsulation in functionalised liposomes showed better efficacy still. The encapsulation of GFLX did not increase the efficacy of GFLX and synergy between the two drugs was not achieved. In conclusion, the liposomal encapsulation of CV7 increased uptake of the drug by the target cell line and facilitated colocalisation of the drug with the target pathogen thereby increasing efficacy. Such a formulation could potentially increase bioavailability and efficacy in vivo for a more tolerable TB therapy.

The aim of this thesis was to find optimal therapy based on combination of membrane-anchored phagocytic ligands (mannose-(G)5-(K)10-STE, mannan-BAM, mannan-SMCC) with LPS (ligand of signal receptor)for treatment of murine melanoma B16-F10. Mixture of mannan-BAM with LPS applied in pulse regime proved to be the most effective, resulting in heigh reduction of tumor growth and significant prolongation of survival.

The aim of this study was to analyze number of incorporated T-DNA harbouring pmi and nptII transgenes and expression of the pmi gene in tomato transformants using Southern blot and Northern blot methods. The presence of a functional PMI protein was assesed using PMI-assay with Chlorophenol red dye. Mannose selection of tomato seeds was established and segregation patterns in T1 progeny were studied.

Made available in DSpace on 2015-03-26T13:52:00Z (GMT). No. of bitstreams: 1 texto completo.pdf: 996773 bytes, checksum: 7322b4697c096a6f17a4388ca498fede (MD5) Previous issue date: 2014-02-17 / Fundação de Amparo a Pesquisa do Estado de Minas Gerais / The L-ascorbic acid (ALA) is produced naturally by plants from D-glucose. Yeasts synthesize a similar metabolite, D-eritroascorbic acid (ADEA). Although this compound does not show activity against scurvy, it contains an antioxidant function, but it is produced in low concentrations by the microorganism. Recently, in order to make yeasts are capable of converting D-galactose D-lactose from cheese whey into ALA, the wild strain Kluyveromyces lactis CBS2359 has been transformed with genes that integrate the L-galactose biosynthesis pathway, isolated from Arabidopsis thaliana. In the presence of intermediate L-galactose, ALA can be synthesized by yeast with enzymes responsible for ADEA production. It has been demonstrated that the engineered strain JVC 1-56 was able to synthesize ALA compared to the wild type, but the yield was still low. In this regard, studies to assist the increased of ALA production are relevant. Once the engineered ALA pathway and native cell wall formation pathway of K. lactis have a common intermediate, GDP-D-mannose, we need to evaluate the effect of uncoupling of vitamin C synthesis route of the growth that requires constant wall synthesis. Moreover, considering the antioxidant properties of ALA, the expectation is that the production of this metabolite increase when JVC 1-56 is exposed to a oxidative stress condition by menadione. In this context, this study investigated the both physiological conditions, using the media Yeast Galactose Base (YGB) and ultrafiltered cheese whey (SQU - byproduct of cheese industry that predominates lactose as carbon source). It was analyzed that Kluyveromyces lactis JVC 1-56 produces higher yields of ALA when it is grown for 96 hours in batch culture in the middle YPGal. Cultivation at low growth rates (0.04 h-1) predisposes the cells to synthesize more ALA per unit cell mass (0.80 mg/mg). However, the yield of continuous culture operated as quimostato, limiting the substrate nitrogen, still proved to be lower than expected in the batch (1.94 mg/mg). Oxidative stress by 12.5 mM menadione on K. lactis JVC1 -56, in the conditions applied, was not effective in the increasing the ALA production (1.47 mg/mg). Still, ADEA yield was higher than ALA in two strategies: 1.37 mg/mg at 0.21 h-1 in culture under steady state, 8.52 mg/mg in batch under oxidative stress and 10.33 mg/mg in the batch in the absence of oxidizing agent, indicating that ADEA may be in a more stable configuration than vitamin C. Finally, the permeate cheese whey remains a prospect for the conversion of lactose into a biotechnological product of higher value aggregate. / O ácido L-ascórbico (ALA) é produzido naturalmente por plantas a partir de D-glicose. Leveduras sintetizam um metabólito semelhante, o ácido D-eritroascórbico (ADEA). Embora este composto não mostre atividade contra o escorbuto, ele contém uma função antioxidante, mas é produzido pelo micro-organismo em baixas concentrações. Recentemente, com a finalidade de fazer as leveduras serem capazes de converter o componente D-galactose da D-lactose do soro de queijo em ALA, a linhagem selvagem de Kluyveromyces lactis CBS2359 foi transformada com genes, que integram a via de biossíntese de L-galactose, isolados de Arabidopsis thaliana. Na presença do intermediário L-galactose, ALA pode então ser sintetizado pela levedura com as enzimas responsáveis pela produção de ADEA. Foi demonstrado que a linhagem engenheirada JVC 1-56 foi capaz de sintetizar ALA em comparação com a selvagem, mas com baixo rendimento. Neste sentido, estudos que auxiliem o aumento da produção de ALA são relevantes. Uma vez que a via engenheirada da síntese de ALA e a via nativa da formação da parede celular de K. lactis possuem um intermediário comum, GDP-D-manose, faz-se necessário avaliar o efeito do desacoplamento da produção de ALA do crescimento que requer constante síntese da parede. Além disso, considerando a propriedade antioxidante do ALA, a expectativa é de que a produção deste metabólito aumentasse quando JVC 1-56 fosse exposta a uma condição de estresse oxidativo por menadiona. Neste contexto, este trabalho investigou as condições fisiológicas mencionadas utilizando os meios Yeast Galactose Base (YGB) e soro de queijo ultrafiltrado (SQU - subproduto de indústrias de queijo em que predomina lactose como fonte de carbono). Foi averiguado que Kluyveromyces lactis JVC 1-56 produz ALA com rendimentos maiores quando cultivada por 96 horas em batelada no meio YPGal. O cultivo em baixas velocidades de crescimento (0,04 h -1) predispõe as células a sintetizar mais ALA por unidade de massa celular (0,80 mg/mg). Entretanto, o rendimento da cultura contínua operada como quimostato, tendo nitrogênio como substrato limitante, ainda mostrou ser inferior ao previsto na batelada (1,94 mg/mg). Já o estresse oxidativo por 12,5 μM de menadiona sobre K. lactis JVC1- 56, nas condições aplicadas, não foi eficaz no aumento da produção de ALA (1,47 mg/mg). Ainda, o rendimento de ADEA foi superior ao de ALA nas duas estratégias: 1,37 mg/mg a 0,21 h-1 na cultura sob regime permanente, 8,52 mg/mg na batelada sob estresse oxidativo e 10,33 mg/mg na batelada na ausência do agente oxidante, indicando que ele pode estar em uma configuração mais estável do que a vitamina C. Finalmente, o permeado do soro de queijo continua sendo uma perspectiva para a conversão da lactose em um produto biotecnológico de maior valor agregado.

Respiratory syncytial virus (RSV) is a major cause of serious lower respiratory tract disease among infants and young children worldwide, and understanding the immune response to its infection is essential for intervention strategies. The innate-response serum mannose-binding lectin (MBL), which recognizes a broad range of pathogens and subsequently activates the complement system, has an essential role in the early phase of infection contributing to the development of an acquired immune response. In this study, 82 children <5 years old with confirmed acute RSV infection and 70 controls had MBL levels measured by an indirect ELISA and PBMC phenotypes characterized by flow cytometry. Samples were distributed in four groups: serum/case (81), serum/control (40), PBMC/case (33), PBMC/control (58). Thirty eight cases were <6 months old and most of them had been interned (33/38). The MBL concentrations from all children presented a wide range of values, however, the greater percentage of cases, i.e. 67.9% (55/81) had <500 ng/mL (low/intermediate) MBL levels compared to 40% (16/40) for control subjects. Case and control MBL levels from children <1 month old were not statistically different, but were substantially lower in cases >24 months old (p=0.034). The CD4+ T cells percentage was lower (p<0.001) in children >6 months old compared to controls, while, the CD8+ T cells percentage in cases and controls was similar except for lower frequency in the 6 12 months old cases (p=0,003). T cell activation (CD3+HLA-II+) was significantly higher in cases compared to controls (p<0,001), in contrast to natural killer cells which were generally decreased (p<0,001). These results suggest that acute RSV infection in these children seems to be associated with low MBL levels, but not interfering in T cell activation. / O virus respiratório sincicial (VRS) é a principal causa de doença do trato respiratório inferior em crianças no mundo todo, principalmente nas menores de seis meses de idade e, compreender a resposta imune contra ele é essencial para desenvolver estratégias de intervenção. A lectina ligante de manose (LLM) do presente no soro, relacionada à resposta imune inata, reconhece uma gama de patógenos, ativa o sistema complemento e tem um papel essencial na fase inicial da infecção, contribuindo para o desenvolvimento de uma resposta adaptativa. Neste estudo, 82 crianças <5 anos de idade com infecção pelo VRS confirmada e 70 controles tiveram os níveis de LLM no soro medidos por um ensaio imuno enzimático indireto e também fenótipos das células mononucleares do sangue periférico (CMSP) caracterizado por citometria de fluxo. As amostras foram distribuidas em quatro grupos: soro/caso (81), soro/controle (40), CMSP/caso (33), CMSP/controle (58). Trinta e oito casos eram <6 meses de idade sendo que a maioria deles foi internada (33/38). As concentrações de LLM em todas as idades tiveram uma ampla distribuição, porém, uma grande porcentagem dos casos, isto é, 67,9% (55/81) tiveram níveis de LLM <500 ng/mL (baixo/intermediário), comparado com 40% (16/40) dos controles. Os nívels de LLM dos casos e controles <1 mês de idade não foram diferentes, mas para as crianças >24 meses de idade, os níveis dos casos foram menores (p=0,034). A porcentagem de células T CD4+ dos casos >6 meses de idade foi menor (p<0.001) do que a dos controles. Ainda, não houve diferença entre casos e controles para as células T CD8+, com excessão da faixa de idade entre 6-12 meses em que os casos apresentaram uma menor freqüência (p=0,003). A ativação de células T (CD3+HLA-II+) foi significativamente maior nos casos do que nos controles (p<0,001), em contraste com as células natural killer que geralmente estiveram diminuidas nos casos (p<0,001). Estes resultados sugerem que a infecção aguda por VRS nessas crianças parece estar associada com baixos nívels de LLM, porém não interferindo na ativação de linfócitos. / Mestre em Imunologia e Parasitologia Aplicada