Abstract
ABSTRACTIn Aggregatibacter actinomycetemcomitans, different serotypes have been described based on LPS antigenicity. Recently, our research group has reported a differential immunogenicity when T lymphocytes were stimulated with these different serotypes. In particular, it was demonstrated that the serotype b of A. actinomycetemcomitans has a stronger capacity to trigger Th1- and Th17-type cytokine production. Objective This study aimed to quantify the expression of different CC chemokines (CCLs) and receptors (CCRs) in T lymphocytes stimulated with the different A. actinomycetemcomitans serotypes. In addition, the expression of the transcription factors T-bet, GATA-3, RORC2, and Foxp3, master-switch genes implied in the Th1, Th2, Th17, and T-regulatory differentiation, respectively, was analyzed in order to determine T-cell phenotype-specific patterns of CCL and CCR expression upon A. actinomycetemcomitans stimulation.Material and Methods Human naïve CD4+ T lymphocytes were obtained from healthy subjects and stimulated with autologous dendritic cells primed with the different A. actinomycetemcomitans serotypes. The expression levels for the chemokines CCL1, CCL2, CCL3, CCL5, CCL11, CCL17, CCL20, CCL21, CCL25, and CCL28, as well as the chemokine receptors CCR1, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, and CCR10 were quantified by qPCR. Similarly, the expression levels for the transcription factors T-bet, GATA-3, RORC2, and Foxp3 were quantified and correlated with the CCL and CCR expression levels.Results Higher expression levels of CCL2, CCL3, CCL5, CCL20, CCL21, CCL28, CCR1, CCR2, CCR5, CCR6, CCR7, and CCR9 were detected in T lymphocytes stimulated with the serotype b of A. actinomycetemcomitans compared with the other serotypes. In addition, these higher expression levels of CCLs and CCRs positively correlated with the increased levels of T-bet and RORC2 when T lymphocytes were stimulated with the serotype b.Conclusion A T-lymphocyte response biased towards a Th1- and Th17-pattern of CCL and CCR expression was detected under stimulation with the serotype b of A. actinomycetemcomitans.
Highlights
In humans, CC chemokines (CCLs) and their speci c CC receptors (CCRs) play a central role in physiological and pathological recruitment of immune cells9,24
Greater levels of CCL3, CCL4, CCL5, CCL28, CCR1, CCR5, and CCR9 were detected in periodontal lesions of aggressive periodontitis patients, and increased levels of CCL2 and CCR4 were found in lesions of chronic periodontitis patients8,23
CD4+ T lymphocytes, were isolated from peripheral blood of healthy donors (Figure 2A). These T lymphocytes activated at a similar extent upon stimulation with dendritic cells primed with the different serotypes of A. actinomycetemcomitans, as shown by the similar signi cant overexpression in CD25D mRNA levels (p
Summary
CC chemokines (CCLs) and their speci c CC receptors (CCRs) play a central role in physiological and pathological recruitment of immune cells. The expression of CCLs and CCRs produces a chemotactic gradient between regional lymph nodes and infected tissues where, depending on the pattern of CCLs and/or CCRs expressed, specific dendritic cells and T lymphocytes are chemoattracted. Th lymphocytes play a central role in the pathogenesis of periodontitis, and a Th1 and Th17dominated immuno-in ammatory response has been associated with periodontal tissue destruction, alveolar bone resorption, and teeth loss In this context, the pattern of CCLs and CCRs expressed by Th lymphocytes is crucial in the establishment of the local Th-pattern of immuno-in ammatory response and in the outcome of the disease. Increased production of IL-4 and IL-10 has been demonstrated to inhibit the production of CCR5 and to induce the expression of CCL11, CCR3, and CCR4, implied in the Th2 lymphocyte differentiation and function
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