Type I interferon production elicits differential CD4+ T-cell responses in mice infected with Plasmodium berghei ANKA and P. chabaudi. (14th October 2021)

• Record Type: Journal Article
• Authors: Ntita, Mbaya; Inoue, Shin-Ichi; Jian, Jiun-Yu; Bayarsaikhan, Ganchimeg; Kimura, Kazumi; Kimura, Daisuke; Miyakoda, Mana; Nozaki, Eriko; Sakurai, Takuya; Fernandez-Ruiz, Daniel; Heath, William R; Yui, Katsuyuki
• Is Part Of: International immunology. Volume 34:Number 1(2022)
• Page Start: 21
• Page End: 33
• Publication Date: 2021-10-14
• Subjects: cytokine -- immunological memory -- malaria -- Tfh -- Th1; Immunology -- Periodicals; 616.079
• DOI: 10.1093/intimm/dxab090
• Languages: English
• ISSNs: 0953-8178

Abstract

Abstract : Type I IFN shapes the CD4+ T cell response to malaria Abstract: Abstract Plasmodium parasites that infect humans are highly polymorphic, and induce various infections ranging from an asymptomatic state to life-threatening diseases. However, how the differences between the parasites affect host immune responses during blood-stage infection remains largely unknown. We investigated the CD4 + T-cell immune responses in mice infected with P. berghei ANKA (PbA) or P. chabaudi chabaudi AS (Pcc) using PbT-II cells, which recognize a common epitope of these parasites. In the acute phase of infection, CD4 + T-cell responses in PbA-infected mice showed a lower involvement of Th1 cells and a lower proportion of Ly6C lo effector CD4 + T cells than those in Pcc-infected mice. Transcriptome analysis of PbT-II cells indicated that type I interferon (IFN)-regulated genes were expressed at higher levels in both Th1- and Tfh-type PbT-II cells from PbA-infected mice than those from Pcc-infected mice. Moreover, IFN-α levels were considerably higher in PbA-infected mice than in Pcc-infected mice. Inhibition of type I IFN signaling increased PbT-II and partially reversed the Th1 over Tfh bias of the PbT-II cells in both PbA- and Pcc-infected mice. In the memory phase, PbT-II cells in PbA-primed mice maintained higher numbers and exhibited a better recall response to the antigen. However, recall responses were not significantly different between the infection groups after re-challenge with PbA, suggesting the effect of the inflammatory environment by the infection. These observations suggest that the differences in Plasmodium -specific CD4 + T-cell responses between PbA- and Pcc-infected mice were associated with the difference in type I IFN production during the early phase of the infection.