Association of myelin peptide with vitamin D prevents autoimmune encephalomyelitis development.

Multiple sclerosis is a chronic, inflammatory and demyelinating disease of the central nervous system (CNS). As there is no cure for this disease, new therapeutic strategies and prophylactic measures are necessary. We recently described the therapeutic activity of the association between myelin oligodendrocyte glycoprotein peptide (MOG) and active vitamin D3 (VitD) against experimental autoimmune encephalomyelitis (EAE). The objective of this work was to evaluate the prophylactic potential of this association in EAE. C57BL/6 mice were vaccinated with MOG in the presence of VitD and then subjected to EAE induction. Animals were euthanized 7 and 19days after disease induction and the following parameters were evaluated: body weight, clinical score, inflammatory process in the CNS, amount of dendritic cells (DCs) and regulatory T cells in the spleen and cytokine production by spleen and CNS cell cultures. Vaccination with MOG associated with VitD determined a drastic reduction in clinical score, body weight loss, CNS inflammation, DCs maturation and also in the production of cytokines by CNS and spleen cell cultures. Collectively, our data indicate that this association prevents EAE development. A similar effect from specific self-antigens associated with VitD is expected in other autoimmune conditions and deserves to be experimentally appraised.

Acute Strongyloides venezuelensis infection did not prevent EAE development: implications for hygiene hypothesis.

Prevalence of allergic and autoimmune pathologies is clearly increasing in developed countries. This has been attributed to a decreased exposure to certain microorganisms and been referred as hygiene hypothesis. In this study we evaluated if a previous infection with Strongyloides venezuelensis would alter the progression of experimental autoimmune encephalomyelitis (EAE) in Lewis rats. Animals were initially infected with 4000 L3 infective larvae of S. venezuelensis by subcutaneous route. Encephalomyelitis was then induced during the acute phase of the infection by immunization with myelin basic protein emulsified with Complete Freund's Adjuvant plus Mycobacterium butyricum. Previous infection downmodulated cytokine production but did not change clinical and histopathological EAE manifestations. Cytometric analysis with antibodies specific for CD4+CD25+Foxp3+ regulatory T cells indicated that infection also did not alter the frequency of these cells in spleen and regional lymph nodes. This finding could partly explain the failure of this worm to avoid EAE progression. Altogether these results demonstrated that infection with S. venezuelensis was not able to modify EAE progression in Lewis rats. In the context of the hygiene hypothesis, these results reinforce the necessity of a comparative study among different helminth species to identify the ones with immunoregulatory competence.

Immunomodulation in human and experimental arthritis: including vitamin D, helminths and heat-shock proteins.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that is mainly directed to the joints, affecting the synovial membrane, the cartilage and also the bone. This disease affects 1% to 2% of the world population and is associated with significant morbidity and increased mortality. RA experimental models have allowed a great deal of information to be translated to the corresponding human disease. This review summarizes some of the most relevant findings targeting immunomodulation in arthritis. Some general guidelines to choose an adequate experimental model and also our experience with arthritis are supplied.

Bacille Calmette-Guérin/DNAhsp65 prime-boost is protective against diabetes in non-obese diabetic mice but not in the streptozotocin model of type 1 diabetes.

Type I diabetes is a disease caused by autoimmune destruction of the beta cells in the pancreas that leads to a deficiency in insulin production. The aim of this study was to evaluate the prophylactic potential of a prime-boost strategy involving bacille Calmette-Guérin (BCG) and the pVAXhsp65 vaccine (BCG/DNAhsp65) in diabetes induced by streptozotocin (STZ) in C57BL/6 mice and also in spontaneous type 1 diabetes in non-obese diabetic (NOD) mice. BCG/DNAhsp65 vaccination in NOD mice determined weight gain, protection against hyperglycaemia, decreased islet inflammation, higher levels of cytokine production by the spleen and a reduced number of regulatory T cells in the spleen compared with non-immunized NOD mice. In the STZ model, however, there was no significant difference in the clinical parameters. Although this vaccination strategy did not protect mice in the STZ model, it was very effective in NOD mice. This is the first report demonstrating that a prime-boost strategy could be explored as an immunomodulatory procedure in autoimmune diseases.

Experimental autoimmune encephalomyelitis evolution was not modified by multiple infections with Strongyloides venezuelensis.

According to the hygiene hypothesis, the increased incidence of allergic and autoimmune diseases in developed countries is mainly explained by the decreased contact between the human population and certain environmental agents as lactobacillus, mycobacteria and helminths. In this study, we evaluated the effect of multiple infections with Strongyloides venezuelensis on the development of experimental autoimmune encephalomyelitis (EAE) in Lewis rats. Multiple infections before EAE induction were not able to change the evolution of the disease. No alterations were observed in weight loss, clinical score and inflammation intensity at the central nervous system. The presence of significant levels of parasite-specific IgG1 but not IgG2b suggested a Th2 polarization. However, the percentage and absolute number of CD4+CD25+Foxp3+ T cells were not changed, being their levels in the spleen and lymph nodes of infected rats comparable to the ones found in normal animals. These results suggest that a Th2-polarized response without concomitant expansion of Foxp3+ regulatory T cells was not able to modify EAE progression. Even though these results do not threaten the hygiene hypothesis, they suggest that this paradigm might be an oversimplification. They also emphasize the need of a study to compare the immunoregulatory ability associated with different helminth spp.

Recovery from Strongyloides venezuelensis infection in Lewis rats is associated with a strong Th2 response.

In this study, we investigated the characteristics of the infection and subsequent immunity induced by Strongyloides venezuelensis in Lewis rats. Animals were infected with 4000 L3 of S. venezuelensis and number of eggs per gram of faeces indicated an acute phase around day 8 and a recovery phase around day 32 after infection. A strong Th2 polarization during recovery phase was ascertained by a significant increase in IgG1 and IgE compared with that in the acute period. A shift in the cytokine profile confirmed these findings. A predominant production of IFN-gamma during the acute phase was followed by IL-10 production during recovery. Together these findings show that experimental infection of Lewis rats with S. venezuelensis presents a kinetics of parasite establishment and immunity similar to that described in other models of helminthic infection.

Impact of malnutrition on immunity and infection

Malnutrition may be a consequence of energy deficit or micronutrient deficiency. It is considered the most relevant risk factor for illness and death, particularly in developing countries. In this review we described the magnitude of this problem, as well as its direct effect on the immune system and how it results in higher susceptibility to infections. A special emphasis was given to experimental models used to investigate the relationship between undernutrition and immunity. Malnutrition is obviously a challenge that must be addressed to health authorities and the scientific community.(AU)