Exploring the functions of NKG7 in CD4⁺ and CD8⁺ T cells during malaria
8 affiliations
- 1QIMR Berghofer Medical Research Institute, Brisbane, Australia
- 2University of Queensland, Brisbane, Australia
- 3Burnet Institute, Melbourne, Australia
- 4University of Bonn, Bonn, Germany
- 5Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
- 6Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia
- 7Infectious Diseases Society Kota Kinabalu Sabah-Menzies School of Health Research Program, Kota Kinabalu, Sabah, Malaysia
- 8Subang Jaya Medical Centre, Selangor, Malaysia
Abstract
Malaria, caused by Plasmodium parasites, is a significant global health issue. CD4+ and CD8+ T cells are important for immunity against Plasmodium infections, but the specific roles of many immune-related effector molecules in T cells remain poorly defined. Here, we investigated the function of NK cell granule protein 7 (NKG7) in T cells during malaria, focusing on its role in CD4+ and CD8+ T cells in Plasmodium blood-stage responses. In a non-lethal malaria model, NKG7 regulated the development of pro-inflammatory T helper 1 (Th1), IL-10-producing type 1 regulatory (Tr1), and T follicular helper cell responses. In a model of cerebral malaria, NKG7 had a cell-intrinsic role in regulating perforin and granzyme B expression, as well as Tr1 cell development. Human investigations involving peripheral blood mononuclear cells from volunteers participating in controlled human P. falciparum malaria infection studies, as well as endemic country patients with P. falciparum and P. vivax malaria, corroborated these findings. High NKG7 expression in T cells from Plasmodium-infected humans was observed, as well as differences in NKG7 expression based on the infecting Plasmodium species. NKG7 expression was associated with both cytotoxic and non-cytotoxic T cells, indicating varied functions following infection. These results advance our understanding about NKG7’s role in T cell-mediated malaria immunity and suggest potential for targeting NKG7 to improve outcomes following Plasmodium infection. Author summary: Malaria remains a major global health burden, and effective immunity depends on coordinated responses by CD4⁺ and CD8 ⁺ T cells. However, the specific molecules that enable these T cells to control infection or contribute to pathology are not fully understood. Here, we investigate the role of NK cell granule protein 7 (NKG7), a molecule associated with cytotoxic function, in T cell responses during malaria. Using mouse models of non-lethal and cerebral malaria, we show that NKG7 is required for optimal development of key CD4 ⁺ T cell subsets, including Th1, IL-10-producing Tr1, T follicular helper, and cytotoxic CD4 ⁺ T cells. In human controlled malaria infection studies and in patients with Plasmodium falciparum or P. vivax malaria, we identify multiple NKG7-expressing CD4⁺ and CD8 ⁺ T cell populations with species-specific patterns. These findings reveal diverse roles for NKG7 in malaria immunity and highlight its potential as a target to modulate host responses.
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BibTeX
@article{frame2026exploring,
title = {{Exploring the functions of NKG7 in CD4⁺ and CD8⁺ T cells during malaria}},
author = {Teija C-M. Frame and Fabian de Labastida Rivera and Nicholas L. Dooley and Jessica A. Engel and Jinrui Na and Yulin Wang and Luzia Bukali and Susanna S. Ng and Patrick T. Bunn and Lynette Beattie and Gunter Hartel and Timothy William and Matthew J. Grigg and Nicholas M. Anstey and James S. McCarthy and Bridget E. Barber and Michelle J. Boyle and Christian R. Engwerda},
journal = {PLOS Pathogens},
year = {2026},
month = sep,
doi = {10.1371/journal.ppat.1013528},
url = {https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1013528},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Exploring the functions of NKG7 in CD4⁺ and CD8⁺ T cells during malaria
AU - Teija C-M. Frame
AU - Fabian de Labastida Rivera
AU - Nicholas L. Dooley
AU - Jessica A. Engel
AU - Jinrui Na
AU - Yulin Wang
AU - Luzia Bukali
AU - Susanna S. Ng
AU - Patrick T. Bunn
AU - Lynette Beattie
AU - Gunter Hartel
AU - Timothy William
AU - Matthew J. Grigg
AU - Nicholas M. Anstey
AU - James S. McCarthy
AU - Bridget E. Barber
AU - Michelle J. Boyle
AU - Christian R. Engwerda
PY - 2026
DA - 2026/09/08
JO - PLOS Pathogens
DO - 10.1371/journal.ppat.1013528
UR - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1013528
AB - Malaria, caused by Plasmodium parasites, is a significant global health issue. CD4+ and CD8+ T cells are important for immunity against Plasmodium infections, but the specific roles of many immune-related effector molecules in T cells remain poorly defined. Here, we investigated the function of NK cell granule protein 7 (NKG7) in T cells during malaria, focusing on its role in CD4+ and CD8+ T cells in Plasmodium blood-stage responses. In a non-lethal malaria model, NKG7 regulated the development of pro-inflammatory T helper 1 (Th1), IL-10-producing type 1 regulatory (Tr1), and T follicular helper cell responses. In a model of cerebral malaria, NKG7 had a cell-intrinsic role in regulating perforin and granzyme B expression, as well as Tr1 cell development. Human investigations involving peripheral blood mononuclear cells from volunteers participating in controlled human P. falciparum malaria infection studies, as well as endemic country patients with P. falciparum and P. vivax malaria, corroborated these findings. High NKG7 expression in T cells from Plasmodium-infected humans was observed, as well as differences in NKG7 expression based on the infecting Plasmodium species. NKG7 expression was associated with both cytotoxic and non-cytotoxic T cells, indicating varied functions following infection. These results advance our understanding about NKG7’s role in T cell-mediated malaria immunity and suggest potential for targeting NKG7 to improve outcomes following Plasmodium infection. Author summary: Malaria remains a major global health burden, and effective immunity depends on coordinated responses by CD4⁺ and CD8 ⁺ T cells. However, the specific molecules that enable these T cells to control infection or contribute to pathology are not fully understood. Here, we investigate the role of NK cell granule protein 7 (NKG7), a molecule associated with cytotoxic function, in T cell responses during malaria. Using mouse models of non-lethal and cerebral malaria, we show that NKG7 is required for optimal development of key CD4 ⁺ T cell subsets, including Th1, IL-10-producing Tr1, T follicular helper, and cytotoxic CD4 ⁺ T cells. In human controlled malaria infection studies and in patients with Plasmodium falciparum or P. vivax malaria, we identify multiple NKG7-expressing CD4⁺ and CD8 ⁺ T cell populations with species-specific patterns. These findings reveal diverse roles for NKG7 in malaria immunity and highlight its potential as a target to modulate host responses.
SN - 1553-7374
ER -