STING activation promotes autologous type I interferon–dependent development of type 1 regulatory T cells during malaria

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Wang, Yulin
De Labastida Rivera, Fabian
Edwards, Chelsea L
Frame, Teija Cm
Engel, Jessica A
Bukali, Luzia
Na, Jinrui
Ng, Susanna S
Corvino, Dillon
Montes de Oca, Marcela
Bunn, Patrick T
Soon, Megan Sf
Andrew, Dean
Loughland, Jessica R
Zhang, Jia
et al.
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2023
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Abstract

The development of highly effective malaria vaccines and improvement of drug-treatment protocols to boost antiparasitic immunity are critical for malaria elimination. However, the rapid establishment of parasite-specific immune regulatory networks following exposure to malaria parasites hampers these efforts. Here, we identified stimulator of interferon genes (STING) as a critical mediator of type I interferon production by CD4+ T cells during blood-stage Plasmodium falciparum infection. The activation of STING in CD4+ T cells by cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) stimulated IFNB gene transcription, which promoted development of IL-10– and IFN-γ–coproducing CD4+ T (type I regulatory [Tr1]) cells. The critical role for type I IFN signaling for Tr1 cell development was confirmed in vivo using a preclinical malaria model. CD4+ T cell sensitivity to STING phosphorylation was increased in healthy volunteers following P. falciparum infection, particularly in Tr1 cells. These findings identified STING expressed by CD4+ T cells as an important mediator of type I IFN production and Tr1 cell development and activation during malaria.

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The Journal of Clinical Investigation

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133

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19

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© 2023, Wang et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.

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Biological sciences

Biomedical and clinical sciences

Health sciences

Cellular immune response

Infectious disease

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Wang, Y; De Labastida Rivera, F; Edwards, CL; Frame, TC; Engel, JA; Bukali, L; Na, J; Ng, SS; Corvino, D; Montes de Oca, M; Bunn, PT; Soon, MS; Andrew, D; Loughland, JR; Zhang, J; et al., STING activation promotes autologous type I interferon–dependent development of type 1 regulatory T cells during malaria, The Journal of Clinical Investigation, 2023, 133 (19), pp. e169417

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