Background: Recent investigations have demonstrated a positive association between periodontitis and pregnancy complications. The purpose of this study was to determine the effect of periodontitis and the subgingival microbial composition on preeclampsia.Methods: A case‐control study was carried out in Cali, Colombia that included 130 preeclamptic and 243 non‐preeclamptic women between 26 to 36 weeks of pregnancy. Sociodemographic data, obstetric risk factors, periodontal status, and subgingival microbial composition were determined in both groups. Preeclampsia was defined as blood pressure ≥140/90 mm Hg, and ≥2+ proteinuria, confirmed by 0.3 g proteinuria/24 hours of urine specimens. Controls were healthy pregnant women. Odds ratios (ORs) for periodontitis and subgingival microbiota compositions were calculated.Results: A total of 83 out of 130 preeclamptic women (63.8%) and 89 out of 243 controls (36.6%) had chronic periodontitis (OR: 3.0; 95% confidence interval (CI): 1.91 to 4.87; P <0.001). Clinical attachment loss increased in the case group (4.0 ± 0.10 mm) compared to the control group (3.0 ± 0.08 mm) (P <0.001). The average newborn birth weight from preeclamptic mothers was 2.453 g, whereas in controls was 2.981 g (P <0.001). Two red complex microorganisms, Porphyromonas gingivalis and Tannerella forsythensis, and the green complex microorganism Eikenella corrodens were more prevalent in the preeclamptic group than in controls (P <0.01).Conclusions: Chronic periodontal disease and the presence of P. gingivalis, T. forsythensis, and E. corrodens were significantly associated with preeclampsia in pregnant women. Further research is needed to establish pathogenic mechanisms of active periodontal disease and subgingival periodontopathogens related to preeclampsia development.

Chronic bone degenerative diseases represent a major threat to the health and well‐being of the population, particularly those with advanced age. This study isolated exosomes (EXO), natural nano‐particles, from dendritic cells, the “directors” of the immune response, to examine the immunobiology of DC EXO in mice, and their ability to reprogram immune cells responsible for experimental alveolar bone loss in vivo . Distinct DC EXO subtypes including immune‐regulatory (regDC EXO), loaded with TGFB1 and IL10 after purification, along with immune stimulatory (stimDC EXO) and immune “null” immature (iDCs EXO) unmodified after purification, were delivered via I.V. route or locally into the soft tissues overlying the alveolar bone. Locally administrated regDC EXO showed high affinity for inflamed sites, and were taken up by both DCs and T cells in situ . RegDC EXO‐encapsulated immunoregulatory cargo (TGFB1 and IL10) was protected from proteolytic degradation. Moreover, maturation of recipient DCs and induction of Th17 effectors was suppressed by regDC EXO, while T‐regulatory cell recruitment was promoted, resulting in inhibition of bone resorptive cytokines and reduction in osteoclastic bone loss. This work is the first demonstration of DC exosome‐based therapy for a degenerative alveolar bone disease and provides the basis for a novel treatment strategy.

Signaling via pattern recognition receptors (PRRs) expressed on professional antigen presenting cells, such as dendritic cells (DCs), is crucial to the fate of engulfed microbes. Among the many PRRs expressed by DCs are Toll-like receptors (TLRs) and C-type lectins such as DC-SIGN. DC-SIGN is targeted by several major human pathogens for immune-evasion, although its role in intracellular routing of pathogens to autophagosomes is poorly understood. Here we examined the role of DC-SIGN and TLRs in evasion of autophagy and survival of Porphyromonas gingivalis in human monocyte-derived DCs (MoDCs). We employed a panel of P. gingivalis isogenic fimbriae deficient strains with defined defects in Mfa-1 fimbriae, a DC-SIGN ligand, and FimA fimbriae, a TLR2 agonist. Our results show that DC-SIGN dependent uptake of Mfa1+P. gingivalis strains by MoDCs resulted in lower intracellular killing and higher intracellular content of P. gingivalis. Moreover, Mfa1+P. gingivalis was mostly contained within single membrane vesicles, where it survived intracellularly. Survival was decreased by activation of TLR2 and/or autophagy. Mfa1+P. gingivalis strain did not induce significant levels of Rab5, LC3-II, and LAMP1. In contrast, P. gingivalis uptake through a DC-SIGN independent manner was associated with early endosomal routing through Rab5, increased LC3-II and LAMP-1, as well as the formation of double membrane intracellular phagophores, a characteristic feature of autophagy. These results suggest that selective engagement of DC-SIGN by Mfa-1+P. gingivalis promotes evasion of antibacterial autophagy and lysosome fusion, resulting in intracellular persistence in myeloid DCs; however TLR2 activation can overcome autophagy evasion and pathogen persistence in DCs. Among the most successful of human microbes are intracellular pathogens. By entering the intracellular milieu, these pathogens are protected from harsh environmental factors in the host, including the humoral and cellular immune responses. Porphyromonas gingivalis is an opportunistic pathogen that colonizes the oral mucosa and accesses the bloodstream and distant sites such as the blood vessel walls, brain, placenta and other organs. Still unclear is how P. gingivalis traverses from oral mucosa to these distant sites. Dendritic cells are highly migratory antigen presenting cells that “patrol” the blood, skin, mucosa and all the major organ systems. Capture of microbes by dendritic cells activates a tightly regulated series of events, including directed migration towards the secondary lymphoid organs, where processed antigens are ostensibly presented to T cells. Autophagy is now recognized as an integral component of microbial clearance, antigen processing and presentation by dendritic cells. We report here that P. gingivalis is able to subvert autophagic destruction within dendritic cells. This occurs through its glycoprotein fimbriae, called Mfa-1, which targets the C-type lectin DC-SIGN on dendritic cells. The other major fimbriae on P. gingivalis, FimA, targets TLR2, which promotes autophagic destruction of P. gingivalis. We conclude that DC-SIGN-TLR2 crosstalk determines the intracellular fate of this pathogen within dendritic cells, and may have profound implications for the treatment of many chronic diseases involving low-grade infections.

Background: The microbial profile of periodontal disease varies among different human populations. This study evaluated the demographic, clinical, and microbiologic aspects of periodontitis in a multigeographic sample in Colombia.Methods: Three hundred twenty‐five patients with chronic periodontitis (CP), 158 patients with aggressive periodontitis (AgP), and 137 healthy‐gingivitis controls from five regions of the country were studied. Clinical, microbial, and sociodemographic data were collected. Microbiologic identification was performed using polymerase chain reaction 16S rRNA gene on pooled subgingival samples, and the presence of Gram‐negative enteric rods was evaluated by culture. Bivariate and multivariate logistic regression analyses were conducted.Results: Porphyromonas gingivalis occurred in 71.5% of individuals with periodontitis, Tannerella forsythensis occurred in 58.5%, Campylobacter rectus occurred in 57.5%, Actinobacillus actinomycetemcomitans occurred in 23.6%, and enteric rods occurred in 34.5%. P. gingivalis was more common in CP and AgP than controls. A. actinomycetemcomitans was increased in AgP compared to controls and patients with CP. T. forsythensis, C. rectus, and Eikenella corrodens had a low presence in the West Pacific and Central regions, and enteric rods were increased in the Central region (P <0.05). Other sociodemographic factors were not associated with these microorganisms.Conclusions: Geographic regions do not influence the microbiota, but the microbiota may vary by geographic region. P. gingivalis, T. forsythensis, and C. rectus are the most prevalent periodontophatic microorganisms in Colombia. A. actinomycetemcomitans was more common in AgP, and a large percentage of the population studied had enteric rods in the subgingival plaque.