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

Abstract

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.

Helminth Infections and Host Immune Regulation

“…Thus, multiple mechanisms may control parasite-specific and bystander immunosuppression. Not all parasitic infections control EAE, however, as infection of rats with Strongyloides venezuelensis did not alter EAE progression by any of the parameters measured (44).…”

Taenia crassicepsInfection Does Not Influence the Development of Experimental Rheumatoid Arthritis

“…Therefore, even when infection is carried out with the same parasite, the outcome of the diseases can greatly vary, as in the case of H. diminuta even when in theory the same disease was being reproduced, although different methods of induction of the disease were used the results reflected an ample spectrum of possibilities. Moreover, another disease where any effect of a helminth infection was not detected was in EAE developed in mice carrying a gastrointestinal infection with Strongyloides venezuelensis [23]. Taken together all these data accumulated on helminth therapy, we suggest that more detailed studies are necessary before “generalize” that any single helminth parasite or their derivatives would be useful for any inflammatory or autoimmune disease.…”

Helminth Products Potently Modulate Experimental Autoimmune Encephalomyelitis by Downregulating Neuroinflammation and Promoting a Suppressive Microenvironment

“…Also, several regulatory cell populations were detected in these trials, such as AAMs and MDSCs; all of them are able to suppress T-cell proliferation, suggesting that the regulation of EAE by a helminth infection work by the induction of such changes in the immune response. Moreover, helminths ability to inhibit CNS infiltration appear to be another immunological trait for the regulation of EAE as the infection with S. venezuelensis [20] was unable to modulate the disease outcome despite being able to induce some of these changes, but unlike the other helminths tested, it could not reduce CNS infiltration. Furthermore, T. crassiceps infection was able to downregulate the development of other inflammatory diseases such as colitis [21] and type 1 diabetes [25] in association with similar regulatory mechanisms, while also arresting the inflammatory infiltration to the target organs, thus suggesting that helminths act to inhibit inflammation in multiple ways, but the deterring of the inflammatory infiltration of the target organs seems to be of paramount importance.…”

“…For instance, Taenia crassiceps [18], Schistosoma mansoni [12], Trichinella spp . [13, 14], Fasciola hepatica [19], and Strongyloides venezuelensis [20] infections have been tested for EAE regulation with different degrees of success, and they were proven to have similar mechanisms of action involved, such as the induction of AAMs, MDSCs, Th2-differentiation, and the induction of low proliferative responses in lymphocytes. Most of these studies were performed in preinfected mice and left unanswered if the disease can be modulated after its onset and whether helminth-derived products are able to supply the infection with the live parasite.…”