RESUMEN
AIM: Destructive periodontitis is associated with a Th1-Th17 immune response and activation of RANKL-induced osteoclasts. In addition, Porphyromonas gingivalis K1 and K2 serotypes induce a strong Th1-Th17 response. This study aimed to investigate whether these P. gingivalis serotypes induce higher osteoclasts activation, by increased Th17-associated RANKL production, and an antigen-specific memory T-lymphocyte response. MATERIAL AND METHODS: The RANKL production and TRAP(+) osteoclast induction were quantified on naïve T lymphocytes stimulated with dendritic cells primed with the P. gingivalis serotypes. The T-bet, GATA-3, RORC2 and Foxp3 expression was correlated with RANKL production. The frequency of proliferating memory T lymphocytes in response to P. gingivalis serotypes was determined in both periodontitis and healthy subjects. RESULTS: T lymphocytes stimulated by K1 or K2-primed dendritic cells elicited higher levels of RANKL and TRAP(+) osteoclasts than cells stimulated with the other serotypes. RANKL positively correlated with RORC2. Whereas periodontitis patients had a higher frequency of memory T lymphocytes responding to K1 or K2, healthy subjects had a higher frequency of memory T lymphocytes responding to K4 or K(-) . CONCLUSIONS: P. gingivalis serotypes K1 and K2, but not others, are associated with an increased production of the osteoclastogenesis-related factor RANKL. This important information suggests that these serotypes could elicit a greater bone resorption in vivo and have a role in the periodontitis pathogenesis.
Asunto(s)
Memoria Inmunológica/inmunología , Osteoclastos/inmunología , Porphyromonas gingivalis/inmunología , Ligando RANK/inmunología , Serogrupo , Linfocitos T/inmunología , Fosfatasa Ácida/análisis , Fosfatasa Ácida/inmunología , Animales , Antígenos Bacterianos/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/microbiología , Diferenciación Celular/inmunología , Línea Celular , Periodontitis Crónica/inmunología , Selección Clonal Mediada por Antígenos , Células Dendríticas/inmunología , Factores de Transcripción Forkhead/análisis , Factor de Transcripción GATA3/análisis , Humanos , Isoenzimas/análisis , Isoenzimas/inmunología , Macrófagos/inmunología , Ratones , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/análisis , Osteoclastos/efectos de los fármacos , Porphyromonas gingivalis/clasificación , Ligando RANK/análisis , Proteínas de Dominio T Box/análisis , Linfocitos T/microbiología , Fosfatasa Ácida Tartratorresistente , Células TH1/inmunología , Células Th17/inmunologíaRESUMEN
AIM: Porphyromonas gingivalis can synthesize an extracellular capsule and different serotypes have been described based on capsular antigenicity. On dendritic cells (DCs), the type of capsule present plays a role on the strength of the developed immune response. This study aimed to investigate the T-lymphocyte responses when stimulated with autologous mature DCs exposed to different P. gingivalis K-serotypes. MATERIALS AND METHODS: Naïve CD4(+) T-lymphocytes were obtained from healthy subjects and stimulated with autologous DCs primed with increasing multiplicity of infections of the different P. gingivalis K-serotypes. The Th1, Th2, Th17 and T-regulatory cytokines and transcription factor levels were quantified. RESULTS: Distinct types of response were detected when T-lymphocytes were stimulated by DCs primed with the different P. gingivalis K-serotypes. T-lymphocytes stimulated by K1 or K2-primed DCs elicited higher levels of Th1 and Th17-associated cytokines, T-bet and RORC2 than T-lymphocytes stimulated with DCs primed with the other serotypes. Conversely, the serotypes K3-K5 induced higher levels of Th2-associated cytokines and GATA-3 than the others. CONCLUSIONS: These results demonstrate that DCs primed with the different P. gingivalis K-serotypes elicited distinct T-cell responses. Strains K1 (W83) and K2 (HG184) induced a Th1/Th17 pattern of immune response and K3 (A7A1-28), K4 (ATCC(®49417™) ), and K5 (HG1690) a Th2 response.
Asunto(s)
Cápsulas Bacterianas/inmunología , Células Dendríticas/microbiología , Porphyromonas gingivalis/inmunología , Linfocitos T/inmunología , Técnicas Bacteriológicas , Citocinas/análisis , Células Dendríticas/inmunología , Factores de Transcripción Forkhead/análisis , Factor de Transcripción GATA3/análisis , Humanos , Interferón gamma/análisis , Subunidad alfa del Receptor de Interleucina-2/análisis , Interleucinas/análisis , Activación de Linfocitos/inmunología , Monocitos/inmunología , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/análisis , Porphyromonas gingivalis/clasificación , Serotipificación , Proteínas de Dominio T Box/análisis , Linfocitos T/microbiología , Linfocitos T Reguladores/inmunología , Células TH1/inmunología , Células Th17/inmunología , Células Th2/inmunología , Factor de Crecimiento Transformador beta1/análisis , Factores de Necrosis Tumoral/análisisRESUMEN
AIM: Capsular polysaccharides play an important role in the virulence of Gram-positive and Gram-negative bacteria. In Porphyromonas gingivalis, six serotypes have been described based on capsular antigenicity and its pathogenicity has been correlated both in vitro and in animal models. This study aimed to investigate the differential response of human dendritic cells (DCs) when stimulated with different P. gingivalis capsular serotypes. MATERIALS AND METHODS: Using different multiplicity of infection (MOI) of the encapsulated strains K1-K6 and the non-encapsulated K(-) strain of P. gingivalis, the mRNA expression levels for interleukin (IL)-1beta, IL-2, IL-5, IL-6, IL-10, IL-12, IL-13, interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, and TNF-beta in stimulated DCs were quantified by real-time reverse transcription-polymerase chain reaction. RESULTS: All P. gingivalis capsular serotypes induced a T-helper type 1 (Th1) pattern of cytokine expression. K1- and K2-stimulated DCs expressed higher levels of IL-1beta, IL-6, IL-12p35, IL-12p40, and IFN-gamma and at lower MOI than DCs stimulated with the other strains. CONCLUSIONS: These results demonstrate a differential potential of P. gingivalis capsular serotypes to induce DC responses and a higher capacity of strains K1 W83 and K2 HG184 than other K serotypes to trigger cytokine expression.