Dendritic cells (DCs) are major immune components, and depending on how these cells are modulated, the protective host immune response changes drastically. Trypanosoma cruzi is a parasite with high genetic variability and modulates DCs by interfering with their capacity for antigen recognition, migration, and maturation. Despite recent efforts, the association between DCs and T. cruzi I (TcI) and TcII populations is unknown. Herein, it was demonstrated that AQ1.7 and MUTUM TcI strains present low rates of invasion of bone marrow-derived DCs, whereas the 1849 and 2369 TcII strains present higher rates. Whereas the four strains similarly induced the expression of PD-L1, the production and expression of IL-10 and TLR-2, respectively, in DCs were differentially increased. The production of TNF-α, IL-12, IL-6, and CCL2 and the expression of CD40, CD80, MHC-II, CCR5, and CCR7 changed depending on the strain. The 2369 strain yielded the most remarkable results because greater invasion correlated with an increase in the levels of anti-inflammatory molecules IL-10 and PD-L1 but not with a change in the levels of TNF-α, MHC-II, or CD40 molecules. These results suggest that T. cruzi strains belonging to different populations have evolved specific evasion strategies that subvert DCs and consequently the host response.

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Chronic periodontitis is a multifactorial inflammatory disease that affects supporting structures of the teeth. Although the gingival response is largely described, little is known about the immune changes in the alveolar bone and neighboring tissues that could indicate periodontal disease (PD) activity. Then, in this study we identified the ongoing inflammatory changes and novel biomarkers for periodontitis in the tissues directly affected by the destructive disease in PD patients. Samples were collected by osteotomy in 17 control subjects during extraction of third molars and 18 patients with advanced PD, in which alveoloplasty was necessary after extraction of teeth with previous extensive periodontal damage. Patients presented mononuclear cells infiltration in the connective tissue next to the bone and higher fibrosis area, along with increased accumulation of IL-17+ and TRAP+ cells. The levels of TNF-α and MMP-2 mRNA were also elevated compared to controls and a positive and significant correlation was observed between TNF-α and MMP-2 mRNA expression, considering all samples evaluated. In conclusion, nongingival tissues neighboring large periodontal pockets present inflammatory markers that could predict ongoing bone resorption and disease spreading. Therefore, we suggested that the detailed evaluation of these regions could be of great importance to the assessment of disease progression.

BackgroundDendritic cells (DCs) are professional antigen-presenting cells with vital roles in the activation of host immunity. Ticks are bloodsucking arthropods that secrete bioactive compounds with immunomodulatory properties via their saliva. It is known that some tick species modulate the biology of DCs with different intensities; however, studies on Amblyomma cajennense, the Cayenne tick, have not yet been performed, although this species is considered one of the most capable of modulating immune responses of different hosts.MethodsEngorged female ticks were stimulated with dopamine to induce salivation, and saliva was pooled. The effects of tick saliva on the biology of dendritic cells were assessed by examining DC differentiation, maturation, migration, cellular viability, cytokine production and expression of surface markers by flow cytometry and ELISA. Competitive enzyme immunoassays (EIA) were used to measure saliva prostaglandin-E2 (PGE2). Statistical significance was determined by ANOVA followed by Tukey’s post-test or by the Kruskal-Wallis test with the Dunns post-test.ResultsIn this work, we demonstrated that the presence of A. cajennense saliva to bone marrow cultures inhibit DC differentiation. This inhibition was not accompanied by inhibition or induction of stimulatory and co-stimulatory molecules such as MHC-II, CD40, CD80 or CD86. Immature and mature DCs that were pre-exposed to saliva showed reduced migration toward the chemokines RANTES and MIP-3β. This inhibition was associated to a reduced expression of CCR5 (the receptor for RANTES) or CCR7 (the receptor for MIP-3β) induced by the presence of saliva in the cultures. Tick saliva also inhibited IL-12p40, IL-6 and TNF-α in a concentration-dependent manner while potentiating IL-10 cytokine production by DCs stimulated with Toll-like receptor-4 ligand. Additionally, A. cajennense tick saliva inhibited the expression of CD40 and CD86 in mature DCs while potentiating the expression of PD-L1. PGE2 was detected as one of the constituents of saliva at a concentration of ~ 80 ng/ml, and we believe that most of the results reported herein are due to the presence of PGE2.ConclusionsThese results help to understand the tick-host interaction and demonstrate that A. cajennense ticks appear to have mechanisms for modulating host immune cells, including DCs.

Morinda citrifolia L. (noni) has been shown to treat different disorders. However, data concerning its role in the treatment of intestinal inflammation still require clarification. In the current study, we investigated the effects of noni fruit juice (NFJ) in the treatment of C57BL/6 mice, which were continuously exposed to dextran sulfate sodium (DSS) for 9 consecutive days. NFJ consumption had no impact on the reduction of the clinical signs of the disease or on weight loss. Nonetheless, when a dilution of 1 : 10 was used, the intestinal architecture of the mice was preserved, accompanied by a reduction in the inflammatory infiltrate. Regardless of the concentration of NFJ, a decrease in both the activity of myeloperoxidase and the key inflammatory cytokines, TNF-α and IFN-γ, was also observed in the intestine. Furthermore, when NFJ was diluted 1 : 10 and 1 : 100, a reduction in the production of nitric oxide and IL-17 was detected in gut homogenates. Overall, the treatment with NFJ was effective in different aspects associated with disease progression and worsening. These results may point to noni fruit as an important source of anti-inflammatory molecules with a great potential to inhibit the progression of inflammatory diseases, such as inflammatory bowel disease.