Dendritic cells treated with crude Plasmodium berghei extracts acquire immune‐modulatory properties and suppress the development of autoimmune neuroinflammation

Abstract

SummaryDendritic cells (DCs) are professional antigen-presenting cells specifically targeted during Plasmodium infection. Upon infection, DCs show impaired antigen presentation and T-cell activation abilities. In this study, we aimed to evaluate whether cellular extracts obtained from Plasmodium berghei-infected erythrocytes (PbX) modulate DCs phenotypically and functionally and the potential therapeutic usage of PbX-modulated DCs in the control of experimental autoimmune encephalomyelitis (EAE, the mouse model for human multiple sclerosis). We found that PbX-treated DCs have impaired maturation and stimulated the generation of regulatory T cells when cultured with naive T lymphocytes in vitro. When adoptively transferred to C57BL/6 mice the EAE severity was reduced. Disease amelioration correlated with a diminished infiltration of cytokine-producing T cells in the central nervous system as well as the suppression of encephalitogenic T cells. Our study shows that extracts obtained from P. berghei-infected erythrocytes modulate DCs towards an immunosuppressive phenotype. In addition, the adoptive transfer of PbX-modulated DCs was able to ameliorate EAE development through the suppression of specific cellular immune responses towards neuro-antigens. To our knowledge, this is the first study to present evidence that DCs treated with P. berghei extracts are able to control autoimmune neuroinflammation.

Protection against Paracoccidioides brasiliensis infection in mice treated with modulated dendritic cells relies on inhibition of interleukin‐10 production by CD8+ T cells

“…However, it is not possible to assume that all crude extracts from a plethora of organisms will induce activation of DCs. In this sense, a previous study from our group showed that Plasmodium berghei extracts down‐modulated DC activity in vitro and adoptive transfer of modulated DCs led to a decreased severity in autoimmune encephalitis . Plasmodium berghei ‐modulated DCs induced the differentiation of regulatory T cells and IL‐10‐producing cells that migrated to the central nervous system of experimental autoimmune encephalomyelitis‐bearing mice.…”

“…For DC modulation, the cells were treated with P. brasiliensis extracts. The preparation of the antigen extracts followed the methods in a previously published paper by our group, with small modifications . Briefly, cultures of P. brasiliensis were prepared for infection with viable fungi, as described above.…”

Violacein Treatment Modulates Acute and Chronic Inflammation through the Suppression of Cytokine Production and Induction of Regulatory T Cells

“…At the 20 th day after EAE induction, mice were anesthetized, perfused with ice cold PBS and the lumbar spinal cords were removed and prepared for the enrichment of infiltrating leukocytes according to a previously described methodology [ 18 , 19 ]. Briefly, spinal cord-derived cells were suspended in Percoll 30%, and then overlaid in Percoll 70%.…”

Nitric oxide plays a key role in the suppressive activity of tolerogenic dendritic cells

“…DC modulation is a possible approach to address the immunosuppression that is often caused by tumors 4 and the exacerbated immune response observed in autoimmune diseases. 5 Multiple sclerosis, one such autoimmune disease, is a debilitating condition that affects the CNS. Studies in EAE, an experimental mouse model of multiple sclerosis, have found that much of the immunological etiology of the disease development is due to the activity of Th1/Th17 cells, and these studies have found that NO plays a major role in disease progression.…”