Resumen de Whole-Blood Cultures From Patients With Chronic Periodontitis Respond Differently to Porphyromonas gingivalis but not Escherichia coli Lipopolysaccharide
Background: Porphyromonas gingivalis lipid A heterogeneity modulates cytokine expression in human cells. This study investigates the effects of two lipid A isoforms of P. gingivalis, lipopolysaccharide (LPS)1435/1449 and LPS1690, on the secretion of proinflammatory and regulatory cytokines in total blood cultures from patients with and without chronic periodontitis (CP).
Methods: A cross-sectional study was conducted in 38 systemically healthy individuals divided in two groups: 1) the CP group (n = 19), in which patients were diagnosed with CP; and 2) the no periodontitis (NP) group (n = 19), which included control patients without CP. Blood samples were collected from all patients, and whole-blood cell cultures (WBCCs) were stimulated for 48 hours with P. gingivalis LPS1435/1449 and LPS1690 and Escherichia coli LPS. Unstimulated WBCCs served as negative controls. The secretion of interferon-? (IFN-?), interleukin-10 (IL-10), and transforming growth factor-ß (TGF-ß) was detected in WBCC supernatants by enzyme-linked immunosorbent assays.
Results: E. coli LPS significantly increased the expression of all cytokines in WBCCs from both the NP and CP groups when compared to non-stimulated cells (control treatment). P. gingivalis LPS preparations increased IFN-? levels in the CP group but not in the NP group when compared with controls (P <0.05). P. gingivalis LPS preparations also increased IL-10 and TGF-ß levels in both CP and NP groups, but P. gingivalis LPS1690 showed a three-fold increase on IL-10 production in the NP group (P <0.05) when compared to P. gingivalis LPS1435/144.
Conclusions: These data demonstrate that WBCC cell populations obtained from healthy individuals and patients with CP may differ in the cytokine response to P. gingivalis but not E. coli LPS. This is consistent with the notion that CP alters the systemic WBCC response and that this can be detected by the different P. gingivalis LPS structures.
Periodontal diseases are initiated by accumulated dental biofilms composed of a complex microbial community of hundreds of different species of bacteria that may act cooperatively.1 The emergence of Porphyromonas gingivalis in such biofilms promotes the severity of periodontal lesions through virulence factors, such as proteases, lipopolysaccharides (LPSs), fimbriae, and volatile sulfur-containing compounds, among others.1 Although a pathogenic oral microbiota is necessary to initiate and exacerbate periodontal disease,2 the degree and severity of this clinical manifestation depend on the way that the different susceptibility components of the host, such as the innate and adaptive immune reactions, mediate local inflammatory responses.2,3 LPS is a major host-interactive surface component of Gram-negative bacteria and one of the most powerful microbial agonists in terms of proinflammatory activities. Recognition of LPS by the host innate immune system could lead to uncontrollable cytokine production, which may contribute to diverse inflammatory diseases in humans. LPS is one of the crucial virulence factors of P. gingivalis, and it is significantly involved in the pathogenesis of periodontal diseases.4 Compared to the well-defined activity of Escherichia coli LPS, P. gingivalis LPS has been shown to be less biologically reactive and to elicit different host responses that are responsible for the mechanisms to evade, or even inhibit, the host immune defense system.5,6 Interestingly, P. gingivalis LPS is highly heterogeneous and contains both tetra-acylated and penta-acylated lipid A structures whose expression is regulated by hemin concentration7 and interacts with Toll-like receptor (TLR)-4.8 The presence of multiple lipid A structures may represent an adaptation of P. gingivalis in response to the alteration of local host microenvironments.7-9 It has been shown that penta-acylated lipid A structures facilitate E-selectin expression, whereas tetra-acylated lipid A structures do not.9 Isoforms of P. gingivalis LPS may conceivably differentially affect host innate immune responses and cytokine production in human gingival epithelia10 and human gingival fibroblasts.11 The present study aims to compare the modulatory effects of P. gingivalis LPS1435/1449 and LPS1690 lipid A structures on the secretion of selected proinflammatory and anti-inflammatory cytokines in cultures of peripheral human whole-blood cells from patients diagnosed with chronic periodontitis (CP).
