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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-?+-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.

SUBMITTER: Thome R

PROVIDER: S-EPMC4201583 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Exacerbation of autoimmune neuro-inflammation in mice cured from blood-stage Plasmodium berghei infection.

Thomé Rodolfo R Bombeiro André Luis AL Issayama Luidy Kazuo LK Rapôso Catarina C Lopes Stefanie Costa Pinto SC da Costa Thiago Alves TA Di Gangi Rosária R Ferreira Isadora Tassinari IT Longhini Ana Leda Figueiredo AL Oliveira Alexandre Leite Rodrigues AL da Cruz Höfling Maria Alice MA Costa Fábio Trindade Maranhão FT Verinaud Liana L

PloS one 20141017 10

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 NK ...[more]

PMID: 25329161

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Project description:The blood-stage of the Plasmodium parasite is one of the key phases within its life cycle that influences disease progression during a malaria infection. The efficiency of the parasite in infecting red blood cells (RBC) determines parasite load and parasite-induced hemolysis that is responsible for the development of anemia and potentially drives severe disease progression. However, the molecular factors defining the infectivity of Plasmodium parasites have not been completely identified so far. Using the Plasmodium berghei mouse model for malaria, we characterized and compared the blood-stage infection dynamics of PbANKA WT and a mutant parasite strain lacking a novel Plasmodium antigen, PbmaLS_05, that is well conserved in both human and animal Plasmodium parasite strains. Infection of mice with parasites lacking PbmaLS_05 leads to lower parasitemia levels and less severe disease progression in contrast to mice infected with the wildtype PbANKA strain. To specifically determine the effect of deleting PbmaLS_05 on parasite infectivity we developed a mathematical model describing erythropoiesis and malarial infection of RBC. By applying our model to experimental data studying infection dynamics under normal and drug-induced altered erythropoietic conditions, we found that both PbANKA and PbmaLS_05 (-) parasite strains differed in their infectivity potential during the early intra-erythrocytic stage of infection. Parasites lacking PbmaLS_05 showed a decreased ability to infect RBC, and immature reticulocytes in particular that are usually a preferential target of the parasite. These altered infectivity characteristics limit parasite burden and affect disease progression. Our integrative analysis combining mathematical models and experimental data suggests that deletion of PbmaLS_05 affects productive infection of reticulocytes, which makes this antigen a useful target to analyze the actual processes relating RBC preferences to the development of severe disease outcomes in malaria.

Dataset Information

Exacerbation of autoimmune neuro-inflammation in mice cured from blood-stage Plasmodium berghei infection.

Publications

Exacerbation of autoimmune neuro-inflammation in mice cured from blood-stage Plasmodium berghei infection.

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