TY - JOUR
T1 - Longitudinal study of changes in γδ T cells and CD4+ T cells upon asymptomatic malaria infection in Indonesian children
AU - De Jong, Sanne E.
AU - Asscher, Vera E.R.
AU - Wammes, Linda J.
AU - Wiria, Aprilianto E.
AU - Hamid, Firdaus
AU - Sartono, Erliyani
AU - Supali, Taniawati
AU - Smits, Hermelijn H.
AU - Luty, Adrian J.F.
AU - Yazdanbakhsh, Maria
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Both γδ T cells and CD4+ T cells have been implicated in immunity to malaria, but their association with natural gain or loss of infection has not been studied before. Therefore, we followed up asymptomatic children living in an area endemic for malaria in Indonesia for 21 months. The percentage of γδ T cells was related to both current and previous infection, with higher percentages in infected than uninfected children and declining after infections resolve. Infected children also had higher levels of Th1 and Th17 cells, lower levels of CD25Hi FOXP3+ regulatory T cells (Tregs), but similar levels of Th2 cells as compared to uninfected children. However, TNF, IFN-γ, and IL-17 cytokine responses to Plasmodium falciparum-infected red blood cells (PfRBCs) were similar, while IL-5 and IL-13 responses were lower in infected children. Furthermore, infected children had more phenotypically exhausted PD-1+ CD4+ T cells, more Tregs expressing TNF-RII, and higher IL-10 responses to PfRBCs, which persisted following resolution of infection. Altogether, this study demonstrates that asymptomatic malaria infection is associated with some long-lasting changes in the frequencies and immunoregulation of circulating innate and adaptive T cells, which might in part explain how pre-exposure to malaria affects responses to subsequent immunological challenges.
AB - Both γδ T cells and CD4+ T cells have been implicated in immunity to malaria, but their association with natural gain or loss of infection has not been studied before. Therefore, we followed up asymptomatic children living in an area endemic for malaria in Indonesia for 21 months. The percentage of γδ T cells was related to both current and previous infection, with higher percentages in infected than uninfected children and declining after infections resolve. Infected children also had higher levels of Th1 and Th17 cells, lower levels of CD25Hi FOXP3+ regulatory T cells (Tregs), but similar levels of Th2 cells as compared to uninfected children. However, TNF, IFN-γ, and IL-17 cytokine responses to Plasmodium falciparum-infected red blood cells (PfRBCs) were similar, while IL-5 and IL-13 responses were lower in infected children. Furthermore, infected children had more phenotypically exhausted PD-1+ CD4+ T cells, more Tregs expressing TNF-RII, and higher IL-10 responses to PfRBCs, which persisted following resolution of infection. Altogether, this study demonstrates that asymptomatic malaria infection is associated with some long-lasting changes in the frequencies and immunoregulation of circulating innate and adaptive T cells, which might in part explain how pre-exposure to malaria affects responses to subsequent immunological challenges.
UR - http://www.scopus.com/inward/record.url?scp=85027708646&partnerID=8YFLogxK
U2 - 10.1038/s41598-017-09099-z
DO - 10.1038/s41598-017-09099-z
M3 - Article
AN - SCOPUS:85027708646
SN - 2045-2322
VL - 7
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 8844
ER -