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Role of IL-10 in inhibiting protective immune responses against infection with heterologous Plasmodium parasites
- Nakamae, Sayuri, Kimura, Daisuke, Miyakoda, Mana, Sukhbaatar, Odsuren, Inoue, Shin-Ichi, Yui, Katsuyuki
- Parasitology international 2019 v.70 pp. 5-15
- CD4-positive T-lymphocytes, Plasmodium berghei, Plasmodium chabaudi, antibodies, antigens, cerebral malaria, cross immunity, cross reaction, drugs, interferon-gamma, interleukin-10, mice, models, parasitemia, parasites, pathogenesis, receptors
- Malaria is induced by infection with Plasmodium parasites, which are genetically diverse, and the immune response to Plasmodium infection has both allele-specific and cross-reactive components. To determine the role of the cross-reactive immune response in the protection and disease manifestation in heterologous Plasmodium infection, we used infection models of P. chabaudi chabaudi (Pcc) and P. berghei ANKA (PbA). CD4+ T cells primed with Pcc infection exhibited strong cross-reactivity to PbA antigens. We infected C57BL/6 mice with Pcc and subsequently treated them with an anti-Plasmodium drug. The Pcc-primed mice exhibited reduced parasitemia and showed no signs of experimental cerebral malaria after infection with PbA. CD4+ T cells from the Pcc-primed mice produced high levels of IFN-γ and IL-10 in response to PbA early after PbA infection. The blockade of IL-10 signaling with anti-IL-10 receptor antibody increased the proportion of activated CD4+ and γδ T cells and the IFN-γ production by CD4+ T cells in response to PbA antigens, while markedly reducing the levels of parasitemia. In contrast, IL-10 blockade did not have a significant effect on parasitemia levels in unprimed mice after PbA infection. These data suggest a potent regulatory role of IL-10 in the cross-reactive memory response to the infection with heterologous Plasmodium parasites leading to the inhibition of the protective immunity and pathogenesis.