Exacerbation of Autoimmune Neuro-Inflammation in Mice Cured from Blood-Stage Plasmodium berghei Infection

Abstract

The thymus plays an important role shaping the T cell repertoire in the periphery, partly, through the elimination of inflammatory auto-reactive cells. It has been shown that, during Plasmodium berghei infection, the thymus is rendered atrophic by the premature egress of CD4+CD8+ double-positive (DP) T cells to the periphery. To investigate whether autoimmune diseases are affected after Plasmodium berghei NK65 infection, we immunized C57BL/6 mice, which was previously infected with P.berghei NK65 and treated with chloroquine (CQ), with MOG35–55 peptide and the clinical course of Experimental Autoimmune Encephalomyelitis (EAE) was evaluated. Our results showed that NK65+CQ+EAE mice developed a more severe disease than control EAE mice. The same pattern of disease severity was observed in MOG35–55-immunized mice after adoptive transfer of P.berghei-elicited splenic DP-T cells. The higher frequency of IL-17+- and IFN-γ+-producing DP lymphocytes in the Central Nervous System of these mice suggests that immature lymphocytes contribute to disease worsening. To our knowledge, this is the first study to integrate the possible relationship between malaria and multiple sclerosis through the contribution of the thymus. Notwithstanding, further studies must be conducted to assert the relevance of malaria-induced thymic atrophy in the susceptibility and clinical course of other inflammatory autoimmune diseases.

Severe Changes in Thymic Microenvironment in a Chronic Experimental Model of Paracoccidioidomycosis

“…The thymic microenvironment integrity must be preserved to ensure the appropriate maturation of T cells since damage to this organ may implicate in inadequate repertoire of T cells in peripheral lymphoid organs, which in turn can lead to autoimmune diseases or immunosuppression. In this context, we have shown that experimental malaria infection leads to thymic atrophy in mice and turns mice susceptible to an aggravated form of experimental autoimmune encephalomyelitis (EAE), the experimental model of multiple sclerosis [ 24 ]. More recently, we found that acute infection with Pb yeast cells promotes thymic alterations that lead to a defective repertoire of peripheral T cells [ 25 ].…”

Tolerogenic Vaccination with MOG/VitD Overcomes Aggravating Effect of C. albicans in Experimental Encephalomyelitis

“…To get evidences for the mechanism that could be involved in this protective effect, we evaluated cytokine production, the percentage of regulatory T cells (Tregs) and myeloid DCs during both the early clinical (10th day) and clinical (17th day) EAE phases. Even though only more recently explored, alterations present at the EAE onset or early clinical disease phase are relevant to determine the involvement and kinetics of different cell types and their mediators in disease aggravation or disease control . The relevance of this early analysis was very clear in our study.…”

Artesunate Ameliorates Experimental Autoimmune Encephalomyelitis by Inhibiting Leukocyte Migration to the Central Nervous System

“…Gene expression analysis was performed as previously described . Briefly, RNA was extracted from tissues using TRIzol reagent according to manufacturer's recommendations (Life Technologies, Carlsbad, CA, USA).…”