β-defensinas como posibles indicadores de la actividad inflamatoria en la enfermedad periodontal / β-defensins as possible indicators of inflammatory activity in periodontal disease

Resumen La enfermedad periodontal (gingivitis y periodontitis) es un proceso inflamatorio ocasionado por la actividad de bacterias patógenas y sus productos sobre el surco gingival, con la consecuente activación de la respuesta inmunitaria. La saliva y el fluido crevicular contienen una gran variedad de enzimas y factores antimicrobianos que están en contacto con la región supragingival y subgingival; entre ellos, las β-defensinas (hBDs). Las hBDs son péptidos catiónicos no glicosilados ricos en cisteína, producidos por las células epiteliales; tienen efecto antimicrobiano e inmunorregulador; de esta forma, contribuyen al mantenimiento de la homeostasis en los tejidos periodontales. Los cambios en la microbiota y en la respuesta inmunitaria de un periodonto sano a gingivitis y, finalmente, a periodontitis, es compleja. Su severidad depende de un equilibrio dinámico entre las bacterias asociadas a la placa, factores genéticos y ambientales. Los avances recientes han permitido comprender la implicación de las hBDs en la detección, el diagnóstico y la terapéutica de la enfermedad periodontal, así como la relación que hay entre la periodontitis y otras enfermedades inflamatorias. El objetivo de esta revisión es describir el efecto de las hBDs en la respuesta inmunitaria y su utilización como marcadores de la actividad inflamatoria de la enfermedad periodontal.

Abstract Periodontal disease (gingivitis and periodontitis) is an inflammatory process caused by the activity of pathogenic bacteria and their products on the gingival sulcus, with the consequent activation of the immune response. Saliva and crevicular fluid contain a wide variety of enzymes and antimicrobial factors that are in contact with the supragingival and subgingival region, including β-defensins (hBDs). hHBDs are non-glycosylated, cysteine-rich cationic peptides produced by epithelial cells with antimicrobial and immunoregulatory effects, thus contributing to maintaining homeostasis in periodontal tissues. The changes in the microbiota and the immune response from a healthy periodontium to gingivitis and, finally, to periodontitis are complex. Their severity depends on a dynamic balance between bacteria associated with plaque, genetic and environmental factors. Recent advances have made it possible to understand the implication of hBDs in the detection, diagnosis, and therapy of periodontal disease and the relationship between periodontitis and other inflammatory conditions. This review aims to describe the effect of hBDs on the immune response and its use as a possible marker of the inflammatory activity of the periodontal disease.

Inhibition of defensin A and cecropin A responses to dengue virus 1 infection in Aedes aegypti / Inhibición de las respuestas de defensina A y cecropina A contra la infección del virus dengue 1 en Aedes aegypti

Abstract | Introduction: It is essential to determine the interactions between viruses and mosquitoes to diminish dengue viral transmission. These interactions constitute a very complex system of highly regulated pathways known as the innate immune system of the mosquito, which produces antimicrobial peptides that act as effector molecules against bacterial and fungal infections. There is less information about such effects on virus infections. Objective: To determine the expression of two antimicrobial peptide genes, defensin A and cecropin A, in Aedes aegypti mosquitoes infected with DENV-1. Materials and methods: We used the F1 generation of mosquitoes orally infected with DENV-1 and real-time PCR analysis to determine whether the defensin A and cecropin A genes played a role in controlling DENV-1 replication in Ae. aegypti. As a reference, we conducted similar experiments with the bacteria Escherichia coli. Results: Basal levels of defensin A and cecropin A mRNA were expressed in uninfected mosquitoes at different times post-blood feeding. The infected mosquitoes experienced reduced expression of these mRNA by at least eightfold when compared to uninfected control mosquitoes at all times post-infection. In contrast with the behavior of DENV-1, results showed that bacterial infection produced up-regulation of defensin and cecropin genes; however, the induction of transcripts occurred at later times (15 days). Conclusion: DENV-1 virus inhibited the expression of defensin A and cecropin A genes in a wild Ae. aegypti population from Venezuela.

Resumen | Introducción. Es esencial determinar las interacciones entre los virus y los mosquitos para disminuir la transmisión viral. Estas interacciones constituyen un sistema muy complejo y muy regulado conocido como sistema inmunitario innato del mosquito, el cual produce péptidos antimicrobianos, moléculas efectoras que funcionan contra las infecciones bacterianas y fúngicas; se tiene poca información de su acción sobre los virus. Objetivo. Determinar la expresión de dos genes AMP (defensina A y cecropina A) en mosquitos Aedes aegypti infectados con el virus DENV-1. Materiales y métodos. Se infectaron oralmente mosquitos de generación F1 con DENV-1 y mediante el análisis con PCR en tiempo real se determinó el potencial papel de los genes defensina A y cecropina A en el control de la replicación del DENV-1 en Ae. aegypti. Como referencia, se infectaron mosquitos con Escherichia coli. Resultados: Los mosquitos no infectados expresaron niveles basales de los ARNm de los genes defensina A y cecropina A en diversos momentos después de la alimentación. Los mosquitos infectados experimentaron una reducción, por lo menos, de ocho veces en la expresión de estos ARNm con respecto a los mosquitos de control en todo el periodo posterior a la alimentación. En contraste con el comportamiento del virus DENV-1, los resultados mostraron que la infección bacteriana produjo una regulación positiva de los genes defensina y cecropina; sin embargo, la inducción de los transcritos ocurrió tardíamente (15 días). Conclusión. El virus DENV-1 inhibió la expresión de los genes defensina A y cecropina A en una población silvestre de Ae. aegypti en Venezuela.

Associação entre beta-defensinas e periodontite / Association between beta-defensins and periodontitis: literature review

Objetivo: as beta-defensinas humanas (hBDs) podem ter um papel-chave na susceptibilidade às doenças na cavidade bucal. Além do efeito antimicrobiano direto, as hBDs aumentam a imunidade adaptativa. O objetivo deste estudo foi realizar uma revisão de literatura científica sobre a relação entre beta-defensinas (hBD) e periodontite. Material e métodos: foi realizada uma pesquisa bibliográfica na base de dados PubMed sobre a expressão de hBDs em indivíduos com periodontite. Os termos beta defensins e periodontitis foram utilizados nessa busca. Resultados: foram selecionados, por um revisor, sete artigos para serem incluídos nessa revisão de literatura: dois estudos de intervenção e cinco estudos transversais. Conclusão: o número de estudos sobre a expressão de beta-defensinas em indivíduos com periodontite é reduzido. O conhecimento sobre o papel das beta-defensinas na periodontite pode trazer um maior entendimento de sua etiopatogenia, além de possibilitar novos indicadores de risco e terapias. Estudos adicionais são necessários para a elucidação da relação entre esses peptídeos antimicrobianos e a periodontite.

Objective: human beta-defensins (hBDs) may play a key role in the susceptibility to diseases in the oral cavity. In addition to the direct antimicrobial effect, hBDs enhance adaptive immunity. The objective of this study was to investigate the literature on the relationship between hBD and periodontitis. Material and methods: a literature review was conducted in the PubMed database on the expression of hBDs in subjects with periodontitis. The terms "beta-defensins" and "periodontitis" were used in this search. Results: seven articles were selected being: two intervention studies and fi ve cross-sectional studies. Conclusion: the number of studies on the expression of beta-defensins in individuals with periodontitis is reduced. Knowledge about the role of beta-defensins in periodontitis may lead to a better understanding of their etiopathogenesis, in addition to providing new risk indicators and therapies. Additional studies are needed to elucidate the relationship between these antimicrobial peptides and periodontitis.

Níveis de beta-defensinas no fluido crevicular gengival de indivíduos com periodontite crônica e Diabetes Mellitus Tipo 2 / Influência da periodontite crônica e do Diabetes Mellitus Tipo 2 nos níveis de beta-Defensinas no fluído crevicular gengival / Crevicular fluid levels of beta-defensins in individuals with chronic periodontitis and type 2 diabetes

Evidências indicam um relacionamento bidirecional entre a periodontite crônica (PC) e o Diabetes Mellitus tipo 2 (DM2). Estudos recentes demonstraram que componentes da resposta imune inata, como as beta-defensinas humanas (hBD), podem apresentar-se alterados em indivíduos com DM2 ou PC. Tendo em vista que a resposta imune inata é a primeira barreira de defesa do organismo, alterações nas hBDs poderiam ser parcialmente responsáveis por um aumento na susceptibilidade dos indivíduos à PC. O presente estudo teve 2 propostas de investigação com objetivos específicos: (1) avaliar a influência da periodontite e da condição inflamatória do sítio nos níveis das hDBs-2 e -3 no fluido crevicular gengival (FCG) de indivíduos com e sem periodontite; e (2) avaliar a influência do DM2 e do controle glicêmico nos níveis das hBDs-1, -2 e -3 no FCG de indivíduos com e sem DM2. Para a proposta 1, foram selecionados indivíduos saudáveis (S) e com periodontite (P) entre os pacientes das clínicas da Faculdade de Odontologia da Universidade Federal de Minas Gerais. Para a proposta 2 foram selecionados indivíduos com DM2 compensados (DM2c) e descompensados (DM2d) entre os usuários do sistema público de saúde da região metropolitana de Belo Horizonte, compreendendo 20 indivíduos em cada grupo. Todos os indivíduos foram submetidos a exame periodontal completo e dados médicos e sociodemográficos foram registrados. Amostras de FCG foram coletadas em sítios saudáveis (Ss) nos indivíduos sem periodontite; amostras de sítios saudáveis (Ps), com gengivite (Pg) e com periodontite (Pp) foram coletadas de indivíduos com periodontite. A quantificação das hBDs no FCG foi realizada pela técnica Enzyme Linked ImmunonoSorbent Assay (ELISA), método de sanduíche. O presente estudo foi aprovado pelo Comitê de Ética em Pesquisa da Universidade Federal de Minas Gerais ­ COEP UFMG (CAAE #0529.0.203.0001-11). Os níveis de hBDs foram comparados entre sítios saudáveis, sítios com gengivite e sítios com periodontite, aninhados em indivíduos com e sem periodontite, através de modelagem hierárquica linear. Os níveis de hBDs foram comparados entre indivíduos saudáveis, DM2c e DM2d por teste de Kruskal-Wallis seguido do teste post-hoc de Dunn para comparações entre os pares. Os resultados mostraram que a periodontite foi associada a elevados níveis de hBD-2 (coeficiente 14,68; p = 0,023) e hBD-3 (coeficiente 1091.86, p < 0.001) no nível indivíduo, no entanto não houve efeito da condição do sítio sobre estes níveis. Foi ainda demonstrado que o DM2, independente do controle glicêmico, foi associado a níveis reduzidos de hBD-1 (p < 0,001), que o DM2 descompensado foi associado com níveis reduzidos de hBD-2 (p < 0,01); e que o DM2 não resulta em alteração nos valores de hBD-3. Uma maior expressão de hBD2 e -3 no FCG de indivíduos com periodontite pode sugerir uma resposta normal do organismo perante à infecção dos tecidos gengivais ou ser considerado um fator parcialmente responsável pela resposta imunoinflamatória exacerbada comumente encontrada nestes indivíduos. O DM2 parecer afetar o padrão de expressão das hBD1 e -2 de maneira distinta.(AU)

Crevicular fluid levels of beta-defensins in individuals with chronic periodontitis and type 2 diabetes Scientific evidence indicates a bidirectional relationship between chronic periodontitis and Type 2 Diabetes Mellitus (DM2). Recent studies have shown that components of the innate immune response, such as human beta-defensins (hBDs), may be altered in individuals with CP or DM2. Given that the innate immune response is the body's first defense barrier against microbial invasion, changes in hBDs could partially account for an increase in the susceptibility CP. The present study had 2 research proposals with specific objectives: (1) to evaluate the influence of periodontitis and inflammatory site condition on hDBs-2 and -3 levels in the gingival crevicular fluid (GCF) of individuals with and without periodontitis; and (2) to assess the influence of DM2 and glycemic control on the levels of hBDs-1, -2 and -3 in the GCF of individuals with and without DM2. For the proposal 1, healthy subjects (H) and subjects with periodontitis (P) were selected among the patients from the School of Dentistry of the Federal University of Minas Gerais. For the proposal 2, individuals with DM2 with good (DM2g) and poor (DM2p) glycemic control were selected among the users of the public health system of the metropolitan area of Belo Horizonte, comprising 20 individuals in each group. All subjects underwent complete periodontal examination and medical and sociodemographic data were recorded. GCF samples were collected in healthy sites (Hh) from subjects without periodontitis; samples of healthy sites (Ph), gingivitis (Pg) and periodontitis (Pp) were collected from individuals with periodontitis. Quantification of hBDs in the GCF was performed by the Enzyme Linked ImmunonoSorbent Assay (ELISA) sandwich method. The present study was approved by the Research Ethics Committee of the Federal University of Minas Gerais - COEP UFMG (CAAE # 0529.0.203.0001-11). Levels of hBDs were compared among healthy sites, sites with gingivitis and sites with periodontitis, nested in individuals with and without periodontitis, through linear hierarchical modeling. Levels of hBDs were compared between healthy subjects, with DM2 with good and poor glycemic control through the Kruskal-Wallis test followed by Dunn's post-hoc test for pair-wise comparisons. Results showed that periodontitis was associated with high levels of hBD-2 (coefficient 14.68, p = 0.023) and hBD-3 (coefficient 1091.86, p <0.001) at the individual level. However, there was no effect of the site condition on these levels. It was also demonstrated that DM2, regardless of the glycemic control, was associated with reduced levels of hBD-1 (p <0.001), that DM2p was associated with reduced levels of hBD-2 (p <0.01); and that DM2 did not result in changes in hBD-3 values. Increased expression of hBD-2 and -3 in the GCF of individuals with periodontitis may suggest either a normal response of the organism to the infection of the gingival tissues or can be considered a partially responsible factor for the exacerbated immunoinflammatory response commonly found in individuals with periodontitis. DM2 appears to affect the expression pattern of hBD-1 and -2 differently.(AU)

An investigation of human beta-defensins and cathelicidin expression in patients with pterygium / Uma investigação da expressão de beta-defensinas humanas e de catelidicina em pacientes com pterígio

ABSTRACT Purpose: To investigate human beta-defensins (HBDs) and cathelicidin LL-37 (LL-37) expressions in patients with pterygium. Methods: In this retrospective consecutive case series, 26 pterygium specimens and 15 normal conjunctival specimens of 15 control subjects were in vestigated. Expressions of HBD-1, HBD-2, HBD-3, and LL-37 were assessed using immuno histochemical staining. A brown color in the cytoplasm and/or nuclei of epithelial cells indicated positive staining for HBDs and LL-37. For each antibody, the intensity of the reaction (negative [-], weak [1+], moderate [2+], or strong [3+]) was determined to describe the immunoreactions. Results: The median age was 52 years in both groups. There were no significant differences in age and sex between the groups (p=0.583, p=0.355, respectively). Of the 26 pterygium specimens, 15 (57.7%) (14 weak, 1 moderate staining) showed HBD-2 expression, which was not observed in any of the control specimens. One (3.8%) pterygium and one (6.7%) control specimen demonstrated weak staining for HBD-3. HBD-2 expression was significantly higher in the pterygium specimens than in the controls (p=0.002). None of the tissue specimens had positive staining for HBD-1 or LL-37 in either group (both; p=1.00). Conclusions: HBD-2 expression was higher in pterygium specimens than in the controls. HBD-2 expression that might be stimulated by inflammatory cytokines may be related to inflammation and fibrovascular proliferation and may play a role in pterygium pathogenesis.

RESUMO Objetivo: Investigar as expressões beta defensinas humanas (HBD) e catelicidina em pacientes com pterígio. Métodos: Nesta série de casos retrospectivos consecutivos, 26 espécimes de pterígio e 15 espécimes conjuntivais normais de 15 indivíduos controle foram investigados. As expressões de HBD-1, HBD-2, HBD-3 e catelicidina (LL-37) foram avaliadas por coloração imuno-histoquímica. Uma cor castanha no citoplasma ou nos núcleos de células epiteliais foi definida como coloração positiva para HBDs e LL-37. Para cada anticorpo foi determinada a intensidade da reação (negativo [-], fraco [1+], moderado [2+] ou forte [3+]) para descrever as imunoreações. Resultados: A idade média foi de 52 anos em ambos os grupos. Não houve diferença significativa entre os grupos em termos de idade e sexo (p=0,583, p=0,355, respectivamente). Das 26 amostras de pterígio, 15 (57,7%) (14 fracas e 1 moderada) demonstraram a expressão de HBD-2 enquanto não foi encontrada em nenhum dos espécimes de controlo. Um dos pterígios (3,8%) e um dos espécimes de controlo (6,7%) demonstraram fraca coloração para HBD-3. A expressão de HBD-2 foi significati vamente maior nos espécimes de pterígio do que nos controles (p=0,002). Nenhum dos espécimes de tecido apresentou coloração positiva para HBD-1 ou LL-37 em ambos os grupos (ambos p=1,00). Conclusão: Encontramos aumento da expressão de HBD-2 em espécimes de pte rígio em relação aos controles. A expressão de HBD-2 que pode ser estimulada por citocinas inflamatórias pode estar relacionada com inflamação e proliferação fibrovascular e pode desempenhar um papel na patogênese do pterígio.

ß-defensin-2 in breast milk displays a broad antimicrobial activity against pathogenic bacteria / ß-defensina 2 no leite materno mostra uma ampla atividade antimicrobiana contra bactérias patogênicas

OBJECTIVE: To describe the antimicrobial activity of ß-defensin-2 produced in the mammary gland and secreted in human breast milk. METHODS: The peptide production was performed by DNA cloning. ß-defensin-2 levels were quantified in 61 colostrum samples and 39 mature milk samples from healthy donors, by an indirect enzyme-linked immunosorbent assay (ELISA). Using halo inhibition assay, this study assessed activity against seven clinical isolates from diarrheal feces of children between 0 and 2 years of age. The activity of ß-defensin-2 against three opportunistic pathogens that can cause nosocomial infections was determined by microdilution test. RESULTS: The peptide levels were higher in colostrum (n = 61) than in mature milk samples (n = 39), as follows: median and range, 8.52 (2.6-16.3) µg/ml versus 0.97 (0.22-3.78), p < 0.0001; Mann-Whitney test. The recombinant peptide obtained showed high antimicrobial activity against a broad range of pathogenic bacteria. Its antibacterial activity was demonstrated in a disk containing between 1-4 µg, which produced inhibition zones ranging from 18 to 30 mm against three isolates of Salmonella spp. and four of E. coli. ß-defensin-2 showed minimum inhibitory concentrations (MICs) of 0.25 µg/mL and 0.5 µg/mL for S. marcescen and P. aeruginosa, respectively, while a higher MIC (4 µg/mL) was obtained against an isolated of multidrug-resistant strain of A. baumannii. CONCLUSIONS: To the authors' knowledge, this study is the first to report ß-defensin-2 levels in Latin American women. The production and the activity of ß-defensin-2 in breast milk prove its importance as a defense molecule for intestinal health in pediatric patients. .

OBJETIVO: Descrever a atividade antimicrobiana da defensina-beta 2 na glândula mamária e secretada no leite materno humano. MÉTODOS: A produção de peptídeos foi realizada por clonagem de DNA. Os níveis de defensina-beta 2 foram quantificados em 61 amostras de colostro e 39 de leite maduro de doadoras saudáveis pelo teste ELISA indireto. Por um ensaio de halo de inibição, avaliamos a atividade contra sete isolados clínicos diarreicos de crianças entre 0 e 2 anos. A atividade da defensina 2 contra três patógenos oportunistas que podem causar infecções nosocomiais foi determinada pelo teste de microdiluição. RESULTADOS: Os níveis de peptídeos estavam significativamente maiores nas amostras de colostro (n = 61) que de leite maduro (n = 39), como segue: 8,52 (2,6-16,3 µg/mL) mediana e faixa em comparação a 0,97 (0,22-3,78), p < 0,0001; teste de Mann-Whitney. O peptídeo recombinante foi obtido da alta atividade antimicrobiana demonstrada contra uma ampla gama de bactérias patogênicas. Sua atividade antibacteriana foi demonstrada em um disco contendo entre 1-4 µg, que produziu zonas de inibição entre 18 e 30 mm contra três isolados de Salmonella spp. e quatro de E. coli. A defensina-beta 2 demonstrou concentrações inibitórias mínimas (CIMs) de 0,25 µg/mL e 0,5 µg/mL para S. marcescen and P. aeruginosa, ao passo que uma CIM maior (4 µg/mL) foi obtida contra um isolado de cepa multirresistente de A. baumannii. CONCLUSÕES: Até onde sabemos, este estudo é o primeiro a relatar níveis de defensina em mulheres da América Latina. A produção e a atividade da defensina 2 no leite materno comprovam sua importância como uma molécula de defesa para a saúde intestinal em pacientes pediátricos. .

ß-defensin-2 in breast milk displays a broad antimicrobial activity against pathogenic bacteria.

OBJECTIVE: To describe the antimicrobial activity of ß-defensin-2 produced in the mammary gland and secreted in human breast milk. METHODS: The peptide production was performed by DNA cloning. ß-defensin-2 levels were quantified in 61 colostrum samples and 39 mature milk samples from healthy donors, by an indirect enzyme-linked immunosorbent assay (ELISA). Using halo inhibition assay, this study assessed activity against seven clinical isolates from diarrheal feces of children between 0 and 2 years of age. The activity of ß-defensin-2 against three opportunistic pathogens that can cause nosocomial infections was determined by microdilution test. RESULTS: The peptide levels were higher in colostrum (n=61) than in mature milk samples (n=39), as follows: median and range, 8.52 (2.6-16.3) µg/ml versus 0.97 (0.22-3.78), p<0.0001; Mann-Whitney test. The recombinant peptide obtained showed high antimicrobial activity against a broad range of pathogenic bacteria. Its antibacterial activity was demonstrated in a disk containing between 1-4 µg, which produced inhibition zones ranging from 18 to 30 mm against three isolates of Salmonella spp. and four of E. coli. ß-defensin-2 showed minimum inhibitory concentrations (MICs) of 0.25 µg/mL and 0.5 µg/mL for S. marcescen and P. aeruginosa, respectively, while a higher MIC (4 µg/mL) was obtained against an isolated of multidrug-resistant strain of A. baumannii. CONCLUSIONS: To the authors' knowledge, this study is the first to report ß-defensin-2 levels in Latin American women. The production and the activity of ß-defensin-2 in breast milk prove its importance as a defense molecule for intestinal health in pediatric patients.

Atopic dermatitis and vitamin D: facts and controversies / Dermatite atopica e vitamina D: fatos e controversias

Patients with atopic dermatitis have genetically determined risk factors that affect the barrier function of the skin and immune responses that interact with environmental factors. Clinically, this results in an intensely pruriginous and inflamed skin that allows the penetration of irritants and allergens and predisposes patients to colonization and infection by microorganisms. Among the various etiological factors responsible for the increased prevalence of atopic diseases over the past few decades, the role of vitamin D has been emphasized. As the pathogenesis of AD involves a complex interplay of epidermal barrier dysfunction and dysregulated immune response, and vitamin D is involved in both processes, it is reasonable to expect that vitamin D's status could be associated with atopic dermatitis' risk or severity. Such association is suggested by epidemiological and experimental data. In this review, we will discuss the evidence for and against this controversial relationship, emphasizing the possible etiopathogenic mechanisms involved.

Pacientes com dermatite atópica têm fatores de risco geneticamente determinados que afetam a função de barreira da pele e as respostas imunes, as quais interagem com fatores ambientais. Clinicamente, isso resulta em uma pele intensamente pruriginosa, inflamada, que permite a penetração de irritantes e alérgenos e predispõe os pacientes à colonização e à infecção por micro-organismos. Dentre os diversos fatores etiológicos responsáveis pelo aumento da prevalência de doenças atópicas nas últimas décadas, o papel da vitamina D tem ganhado destaque. Uma vez que a patogênese da dermatite envolve uma interação complexa da disfunção da barreira epidérmica e desregulação da resposta imune - e a vitamina D está envolvida em ambos os processos-, é razoável esperar que a vitamina D esteja associada ao risco ou à gravidade da dermatite atópica. Tal associação é sugerida por dados epidemiológicos e experimentais. Nessa revisão, serão abordadas as evidências favoráveis e contrárias a essa polêmica relação, enfatizando os possíveis mecanismos etiopatogênicos envolvidos.

Cavidad oral: importante sitio de vigilancia inmunológica / Oral cavity: important site for immune surveillance

La cavidad oral es el principio del tracto digestivo y uno de los sitios del cuerpo más expuestos al ingreso de todo tipo de patógenos, tanto del aire como de los alimentos. Aunque varios excelentes artículos han examinado distintos aspectos de tejidos linfoides asociados a mucosas (MALT), no hay suficiente información acerca de la respuesta inmune en la cavidad oral. En esta revisión destacamos algunos aspectos sobre la anatomía / histología de la cavidad oral, estructuras asociadas y células o moléculas con crucial función inmunológica contra antígenos que ingresan en la boca. Los estudios sobre la mucosa oral han adquirido mucha notoriedad últimamente debido a que ofrece una excelente accesibilidad y evita la degradación de las proteínas y péptidos. En la cavidad bucal se puede generar una respuesta inmune apropiada contra microorganismos, en donde además de la IgA salival muchas otras moléculas son liberadas y cumplen un rol protagónico. A pesar de todos estos factores de defensa, existen momentos en donde el individuo se encuentra más expuesto, dependiendo de la edad, factores hormonales, genéticos, hábitos de fumar y la actividad física, ya que todo esto modifica la tasa de flujo salival, tasa de secreción y concentración de IgA salival y demás proteínas. (AU)

The oral cavity is the beginning of the digestive tract and one of the most exposed body sites to the entry of all types of pathogens in the air as food. Although several excellent articles have examined various aspects of mucosa-associated lymphoid tissue (MALT), there is insufficient information about the oral cavity immune response. In this review we highlight some aspects of the anatomy / histology of the oral cavity, associated structures and cells or molecules with crucial immunological function against antigens that enter the mouth. Studies on the oral mucosa have gained much notoriety lately because it offers excellent accessibility and prevents the degradation of proteins and peptides. In the oral cavity can generate an appropriate immune response against microorganisms, where salivary IgA in addition to many other molecules are released and play a role. Despite these defense factors, there are moments where the individual is more exposed, depending on age, hormonal factors, genetic, smoking habits and physical activity, and that this changes the rate of salivary flow rate secretion and concentration of salivary IgA and other proteins.(AU)

Defensinas de paantas y su uso potencial como controladores de plagas en la agricultrra / Plant Defensins and Their Potential Use as Pest Control in Agriculture

RESUMEN Las plantas, al igual que todos los organismos de la naturaleza, poseen elaborados sistemas de defensa contra patógenos, que pueden ser físicos y químicos, y producirse de forma constitutiva e inducida. Dentro de las barreras químicas inducidas se encuentra el grupo de proteínas de bajo peso molecular denominadas péptidos antimicrobianos (AMPs), al cual pertenecen las defensinas, péptidos con peso molecular entre 5 a 7 kDa, punto isoeléctrico de 9, y longitud de 45 a 55 aminoácidos; que tienen la capacidad de inhibir efectivamente el crecimiento de microorganismos fitopatógenos, en su mayoría hongos, y además, generan resistencia a condiciones abióticas de estrés en plantas. Este texto pretende realizar una descripción clara y actual de las características e investigaciones recientes con relación a las defensinas de plantas y sus más destacados usos en el control de patógenos en cultivos de importancia económica. Se plantea además la necesidad de profundizar en el conocimiento de dichas proteínas para su uso en estrategias de control tales como la producción de plantas y microorganismos transgénicos.

ABSTRACT Plants, as all organisms in nature, have elaborate systems of defense against pathogens; which can be physical or chemical and produced in a constitutive and induced way. Among the induced chemical barriers, there is a group of low molecular weight proteins, known as antimicrobial peptides (AMPs). These peptides include defensins, which are peptides with a molecular weight about 5 to 7 kDa, isoelectric point of 9, and length of about 45 to 55 amino acids. Likewise, they have the ability to avoid the growth of phytopathogenic microorganisms, mainly funguses. Moreover, these peptides create resistance to abiotic conditions of stress in plants. This manuscript seeks to make a clear and current description about the recent characteristics and researches related to plant defensins and their most significant uses in pathogens management in crops of economical relevance. It also intends to go deep into the study of such proteins in order to use them as a control strategy, such as production of transgenic plants and microorganisms.

Péptidos antimicrobianos: [revisión] / Antimicrobial peptides: [review]

Los péptidos antimicrobianos son las moléculas efectoras del sistema inmune innato, cuyas familias se encuentran en casi todos los organismos, desde bacterias hasta mamíferos. Son una familia de sustancias polifacéticascon complejos mecanismos deacción relacionados con la interacción con el patógeno a través de su membrana, o afectando blancos internos, como la replicación del ADN y la síntesis de proteínas, e interactuando con el huésped con funciones inmunomoduladoras de la regulación delproceso inflamatorio y de la cicatrización. Aunque la generación de resistencia a los péptidos antimicrobianos es mucho menorsi se compara con la generada por losantibióticos convencionales, existen mecanismos de resistencia ya descritos, como la degradación por proteasas, la liberación de proteínas inhibidoras o los cambios en la conformación de la membrana externa del patógeno. El estudio de estas sustancias hapermitido evidenciar sus usos potenciales en el ámbito clínico para contrarrestar los inconvenientes de la resistencia a los antibióticos; sin embargo, a pesar de los grandesavances logrados en este campo, aún quedan puntos controversiales por dilucidar.

The antimicrobial peptides (AMP) are theeffectors molecules of the innate immunesystem, finding groups of this kind of substances in almost all living organisms from bacteria to mammals. They are a family of versatile substances with complexes action mechanisms in the pathogen they interact with membrane, DNA synthesis and protein synthesis and folding, and also with the hostshowing immunomodulatory functions inwound healing and inflammation process.Even though the generation of resistance to the AMP is lower compare with conventional antibiotics there are resistance mechanism already describe to this kind of substances like degradation by proteases, releasing ofinhibitory substances or conformationalchanges in the external membrane of thepathogen. Actually the study of this group of substances has make them see as potential tools for clinical use helping to coun-teract the problem of antibiotic resistance, but even great progress had been made in this field there still exist some controversial issues for future study.

Defensinas humanas: profilaxis y terapia contra el VIH? / Human defensins: prophylaxis and therapy against HIV?

Las defensinas humanas son péptidos antimicrobianos de síntesis endógena, con potencial profiláctico y terapéutico anti VIH. La aplicación de las defensinas como agentes tópicos en mucosas expuestas podría bloquear la entrada del VIH, debido a la capacidad de estos péptidos de unirse a la envoltura viral. Además, la capacidad de las defensinas para inhibir la replicación del virus, activar el sistema del complemento y quimiotaxis hacia células dendríticas y células T de memoria, permitirá diseñar mejores drogas antiretrovirales, siendo necesario evaluar la eficacia de las defensinas en la práctica clínica.

Human defensins are endogenous antimicrobial peptides with prophylactic and therapeutic potential against HIV. The ability of defensins to bind the HIV envelope could be exploited to design topic agents that block viral entry into exposed mucosa. Additionally, their capacity to inhibit viral replication, complement system activation, dendritic and memory T cells chemoattraction, together with peptide engineering could bring about new and better antiretroviral drugs. Clinical trials could be demonstrated the efficacy of defensins against HIV in clinical practice.

Papel de las células epiteliales en la respuesta inmune del pulmón / Immunological role of epithelial cells of the lung

El sistema respiratorio se encuentra en contacto con agentes patógenos; sin embargo, gracias a la respuesta inmune innata de éste, sólo en raras ocasiones se produce la enfermedad. Las células epiteliales del tracto respiratorio desempeñan un papel importante para evitar la colonización del pulmón por agentes infecciosos, identificando a los microorganismos a través de receptores especializados como los toll-like. Asimismo, son capaces de secretar citocinas, péptidos antimicrobianos y otras moléculas proinflamatorias, las cuales evitan el establecimiento de patógenos.

The respiratory tract is one of the main systems which is in perennial contact with a wide variety of pathogenic microorganisms; however, infection is seldom produced due to its innate immune response. Respiratory tract epithelial cells play a very important role to avoid colonization of the lung by infectious agents, because they recognize microbial molecules through very specialized receptors, such as toll-like receptors; moreover, these cells posses a broad variety of molecules which are related to local immunity. Respiratory tract epithelial cells produce chemokines, antimicrobial peptides and other proinflammatory molecules that prevent the establishment of pathogenic microorganisms.

PROTEÍNAS ANTIFÚNGICAS CONTRA P. INFESTANS EN LOS ESPACIOS INTERCELULARES DE HOJAS DE TOMATE (Lycopersicon esculentum cerasiforme) POSIBLES DEFENSINAS DE PLANTAS / ANTIFUNGAL PROTEINS AGAINST P. INFESTANS FROM INTRACELLULAR SPACE OF TOMATO LEAVES (Lycopersicon esculentum cerasiforme) POSSIBLE DEFENSINS OF PLANTS

Se aislaron y caracterizaron parcialmente proteínas antifúngicas de los espacios intercelulares de hojas de tomate Lycopersicon esculentum cerasiforme, variedad que ha mostrado resistencia en campo a Phytophthora Infestans; se observó que después de inoculación con el patógeno dichas proteínas se acumularon sistémicamente en la planta. Las proteínas identificadas mostraron características de Defensinas de plantas, una nueva familia de proteínas con bajo peso molecular, carga positiva a pH fisiológico y actividad antifúngica evaluada in vitro contra P. infestans. Los análisis electroforéticos en geles de poliacrilamida con SDS-Tricina en condiciones reductoras y no reductoras, sugirieron que están asociadas en trímeros y tetrámeros y poseen pesos moleculares de 5,2 kDa.

Antifungal Proteins from intercellular space of Tomato leaves Lycopersicon esculentum cerasiforme were isolated and partially characterized; this variety had shown resistance against Phytophthora infestans, after inoculating plants with the pathogen it was observed that these proteins were accumulated systemically. The isolated proteins be haved as plant defensins, a novel protein family, with low molecular weight, cationics at physiological pH and Antifungal Activity in vitro evaluated against P. infestans. Electrophoretic analyses in SDS Tricine-PAGE, under reducing and non-reducing conditions suggested that, they were associated as trimers and tetramers; and have molecular weights of 5,2 kDa.