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Biomedical subjects

B R Ferreira

Publications and source records attributed to B R Ferreira.

6 recordsLinked to original sources
PubMed2007

The dual role of p55 tumour necrosis factor-alpha receptor in Actinobacillus actinomycetemcomitans-induced experimental periodontitis: host protection and tissue destruction.

Inflammatory immune reactions in response to periodontopathogens are thought to protect the host against infection, but may trigger periodontal destruction. Thus, we examined the mechanisms by which the proinflammatory cytokine tumour necrosis factor (TNF)-alpha modulates the outcome of Actinobacillus actinomycetemcomitans-induced periodontal disease in mice. Our results showed that TNF-alpha receptor p55-deficient mice [p55TNF-knock-out (KO)] developed a less severe periodontitis in response to A. actinomycetemcomitans infection, characterized by significantly less alveolar bone loss and inflammatory reaction. Real-time polymerase chain reaction (PCR) demonstrated that levels of chemokines (CXCL1, 3 and 10; CCL3 and 5) and their receptors (CXCR2 and 3, CCR5) were lower in p55TNF-KO mice, as were matrix metalloproteinase (MMP)-1, 2 and 9 and receptor activator of nuclear factor kB ligand (RANKL) mRNA levels. However, the absence of the TNF-alpha p55 results in an impairment of protective immunity to A. actinomycetemcomitans infection, characterized by increased bacterial load and higher levels of C-reactive protein during the course of disease. Such impaired host response may be the result of the reduced chemoattraction of lymphocytes, neutrophils and macrophages, and reduced inducible nitric oxide synthase expression (iNOS) and myeloperoxidase (MPO) production in periodontal tissues of p55 TNF-KO mice. Our results demonstrate the mechanisms involved determining periodontal disease severity by TNF-alpha receptor p55, and its role in providing immune protection to A. actinomycetemcomitans periodontal infection.

Actinobacillus Infections↗
PubMed2006

Cytokine pattern determines the progression of experimental periodontal disease induced by Actinobacillus actinomycetemcomitans through the modulation of MMPs, RANKL, and their physiological inhibitors.

OBJECTIVE: Inflammatory and immune reactions raised in response to periodontopathogens are thought to trigger periodontal tissue destruction. We therefore investigated the expression of matrix metalloproteinases (MMPs) and the osteoclastogenic factor RANKL (receptor activator of nuclear factor-kappaB ligand), their respective inhibitors TIMPs (tissue inhibitors of metalloproteinases) and OPG (osteoprotegerin) and their possible correlation with the expression of inflammatory and regulatory cytokines in the course of experimental periodontal disease in mice. METHODS: We characterized the time course of leukocyte migration and alveolar bone loss in C57BL/6 mice infected with Actinobacillus actinomycetemcomitans. Quantitative polymerase chain reaction (RealTime PCR) and ELISA were performed to determine the expression of MMPs, TIMPs, RANKL, OPG and cathepsin K, interleukin-1beta, tumor necrosis factor-alpha, interferon-gamma, interleukin-12, interleukin-4 and interleukin-10 in periodontal tissue samples harvested throughout the course of experimental disease. RESULTS: Oral inoculation of A. actinomycetemcomitans results in an intense and widespread migration of leukocytes to the gingival tissues, besides marked alveolar bone resorption. Our data also demonstrate two distinct patterns of MMP/TIMP and RANKL/OPG expression in the course of experimental periodontal disease. The expression of MMPs (MMP-1, 2 and 9) and RANKL was correlated with the expression of interleukin-1beta, tumor necrosis factor-alpha and interferon-gamma, in a time period characterized by the intense increase of inflammatory reaction and alveolar bone loss. On the other hand, interleukin-4 and interleukin-10 were associated with higher expression of TIMPs (TIMP 1, 2 and 3) and OPG, with a lower expression of MMPs and RANKL, and with reduced rates of increase of cellular infiltration in periodontal tissues and alveolar bone loss. CONCLUSIONS: It is possible that the pattern of cytokines produced in periodontal tissues determines the progression and the severity of experimental periodontal disease, controlling the breakdown of soft and bone tissues through the balance between MMPs/TIMP and RANKL/OPG expression in gingival tissues.

Actinobacillus Infections↗
PubMed1999

Successive tick infestations selectively promote a T-helper 2 cytokine profile in mice.

Several studies have revealed that T lymphocytes and cytokines play a crucial role in determining the outcome of parasitic infections in terms of protective immunity. In this study we found that Rhipicephalus sanguineus tick saliva stimulates transforming growth factor-beta (TGF-beta), and reduces interleukin-12 (IL-12) secretion by cells from normal C3H/HeJ mice. Moreover, murine lymph node cells harvested 6 days after the fourth infestation with ticks presented an 82.4% decrease in their proliferative response to concanavalin A (Con A) compared with the response of control cells. In addition, lymph node cells cultured in the presence of Con A showed a T-helper 2-type (Th2-type) cytokine profile, represented by augmented IL-4 and IL-10 and TGF-beta. On the other hand, the IL-2, interferon-gamma (IFN-gamma) and IL-12 synthesis was significantly inhibited. These results indicate that ticks may modulate the host's immune response through saliva injection. Considering that C3H/HeJ mice develop no protective immunity to R. sanguineus infestation, our results suggest that tick-induced Th2-type cytokines and a decreased proliferative response probably lead the host to a susceptible state to both tick and tick-transmitted pathogens.

Animals↗
PubMed1998

Saliva of Rhipicephalus sanguineus tick impairs T cell proliferation and IFN-gamma-induced macrophage microbicidal activity.

In this study, we investigated tick saliva effects on T cell proliferation, antigen presentation and IFN-gamma-induced macrophage activation, events which are associated with host immune defense mechanisms. Mice repeatedly infested with Rhipicephalus sanguineus ticks, similarly to dogs, did not develop resistance to further infestations. We determined that R. sanguineus tick saliva inhibited, in a dose-dependent manner, both Con-A and specific antigen-induced splenic T cell proliferation. Tick saliva diluted twenty times (64 microg/ml) inhibited Con-A-induced and antigen-specific T cell proliferation in 83% and 69%, respectively. In addition, the inhibition of cell proliferation correlated with a decrease in IL-2 production. Microconcentrator fractionated saliva was tested on a Con-A-induced cell proliferation assay, and showed that one fraction between 3 and 10 kDa and another smaller than 3 kDa can be responsible for the inhibition of T cell proliferation. Although saliva inhibited cell proliferation, it did not impair antigen presentation. Tick saliva further abrogated the killing of intracellular forms of Trypanosoma cruzi by IFN-gamma-activated macrophages. Moreover, saliva-induced macrophage inhibition of IFN-gamma-induced-trypanocidal activity was paralleled with 69% less nitric oxide (NO) production. Finally, tick saliva doubled the production of IL-10 and reduced 84.6% production of IFN-gamma by splenocytes cultured with T. cruzi, suggesting that decreased macrophage NO production may be due to a saliva-induced cytokine imbalance, leading to decreased NO synthase activity. Together, these data indicate that tick saliva can modulate host immune response, thus, contributing to its feeding success and favoring the transmission of tick-borne pathogens.

Animals↗
PubMed1996

Western blot analysis of tick antigens from a Rhipicephalus sanguineus unfed larval extract and identification of antigenic sites in tick sections using immunohistochemistry. A comparative study between resistant and susceptible host species.

Most parasite-host relationships are characterized by the development of resistance by the host, thus limiting the number of parasites. However, some cases are very unusual. In the relationship of the domestic dog with the brown dog-tick Rhipicephalus sanguineus this does not occur, whereas guinea pigs develop efficient resistance. Sera from domestic dogs, crab-eating foxes and guinea pigs collected before and after infestation with R. sanguineus ticks, and after immunization with a whole tick adult or larval homogenate, were used in Western blot analysis to compare and identify potential important antigens from a tick larval homogenate. The same sera were tested in an indirect immunohistochemistry assay in an attempt to compare relevant antigenic sites on histological tick sections. The immunoblotting displayed antigens recognized only by the guinea pigs, as well as several shared antigens between host species, depending on the king of immunization. Immunohistochemistry revealed probable antigenic sites on the cells and tissues of ticks, which varied depending on the kind of immunization (infestation or vaccination) and the animal species involved.

Animals↗