Tesis Doctorado
Respuesta inmune durante la periódontitis: variabilidad de la respuesta de celulas dendriticas y linfocitos t frente a bacterias periódontales.
Autor
Vernal-Astudillo, Rolando
Institución
Resumen
Penodontitis represents a heterogenic group of periodontal infections elicited by
bacteria residing at the subgingival biofilm. Although this biofilm is constituted by a
broad variety of bacterial species, only a limited number has been associated with the
periodontitis aetio!ogy, among them Porphyromonas gingivalis and Aggregatibacter
actinornvcetemcomilans. Both P. gingivalis and A. actinornvcetemcomitans express a
number of virulence factors that contribute to direct tissue damage; however, their
pathogenicity relies mainly on the induction of a host immuno-inflammatory
response. This Ieads to the release of a broad array of cytokines, chemokines and
inflammatory mediators, which cause destruction of the tooth-supporting tissues and
ultimately tooth loss. The data regarding the immune response developed during
periodontitis remains controversial. In fact, severa! authors have hypothesized that
active periodontitis is associated with a T helper type-! (ThI) host response, whi!e
others have suggested that periodontitis is a Th2-associated disease. Additionally, a
Thl 7-type of response has reccntly been associated with. periodontitis-induced tissue
destruction; however, the role of the T regu!atory (Treg) response has not been
complete!y established. In the present investigation, first at ah, the role of Treg cehis
and the immunoregulatory cytokines in progressive periodontitis were analyzed. Our
data suggest that Foxp3 CD4 T cells that do not exert their regulatory function
expressing CTLA-4, IL-lO and TGF-3! play a role in the pathogenesis of active
periodontal !esions during progressive periodontitis. Due to the Th response
developed during the periodontal infection depend.s, a! !east in part, on the number
and type of pathogenic bacteria colonizing the subgingival pocket and invading the
periodontal tissues, the expression of costimulatory mo!ecules and cytokines was
ana!yzed in dendritic ce!!s (DCs) stimulated with different bacterial concentration of
P. gingivalis and A. actinornvcetemcomitans. Quantitative differences in the response
of DCs against P. gingivalis and A. actinomycetemcomilans were detected. Finahly,
in order to determine whether different P. gingivalis serotypes might lead to a
differentia! T !ymphocyte activation and response, the synthesis of cytokines and the
expression of transcription factors T-bet, GATA-3, RORC2 and Foxp3, the masterswitch
genes contro!hing the Th!, Th2, Th17, and Treg cdl differentiation, respcctivcly, wcre analyzed on human T lymphocytes activated with different P.
gingivalis capsular (K) scrotypes. Hereby demonstrating that P. gingivalis Kl and
K2 triggcr a Th 1 fTh 17 phenotype and response on T lymphocytes, serotypes K3, K4
and K5 trigger a Th2 response and the K strain a Treg phenotypc. Furthermore, T
cclls responding to Kl or K2, but not to the othcr serotypes, Lcd to an increased
secretion of RANKL, a key cytokine invoLved in alveolar bone resorption. Taken
together, these data dcmonstratc that the capsule expressed by P. gingivalis
determine the activation of DCs and the effector response of T lymphocytes and
allowed to suggest that serotypes Kl and K2 of P. gingivalis are associated to thc
bone destruction observed during periodontitis. PFCHA-Becas Doctor 168p. PFCHA-Becas TERMINADA