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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Parasite Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1433904

NK cells contribute to the resolution of experimental malaria-associated acute respiratory distress syndrome after antimalarial treatment

Provisionally accepted
Emilie Pollenus Emilie Pollenus 1Hendrik Possemiers Hendrik Possemiers 1Sofie Knoops Sofie Knoops 1Fran Prenen Fran Prenen 1Leen Vandermosten Leen Vandermosten 1Thao-Thy Pham Thao-Thy Pham 1Laura Buysrogge Laura Buysrogge 1Patrick Matthys Patrick Matthys 2Philippe E. Van den Steen Philippe E. Van den Steen 1*
  • 1 Laboratory of Immunoparasitology, Department of Microbiology, Immunology and Transplantation, Rega Institute of Medical Research, KU Leuven, Leuven, Belgium
  • 2 Department of Microbiology and Immunology, Rega Institute for Medical Research, KU ?Leuven, Leuven, Belgium

The final, formatted version of the article will be published soon.

    In both humans and mice, natural killer (NK) cells are important lymphocytes of the innate immune system. They are often considered pro-inflammatory effector cells, but may also have a regulatory or pro-resolving function by switching their cytokine profile towards the production of anti-inflammatory cytokines, including interleukin-10 (IL-10) and transforming growth factor-β, and by killing pro-inflammatory immune cells. Here, the role of NK cells in the resolution of malaria lung pathology was studied. Malaria complications, such as malaria-associated acute respiratory distress syndrome (MA-ARDS), are often lethal despite the rapid and efficient killing of Plasmodium parasites with antimalarial drugs. Hence, studying the resolution and healing mechanisms involved in the recovery from these complications could be useful to develop adjunctive treatments. Treatment of Plasmodium berghei NK65-infected C57BL/6 mice with a combination of artesunate and chloroquine starting at the appearance of symptoms was used as a model to study the resolution of MA-ARDS. The role of NK cells was studied using anti-NK1.1 depletion antibodies and NK cell-deficient mice. Using both methods, NK cells were found to be dispensable in the development of MA-ARDS, as shown previously. In contrast, NK cells were crucial in the initiation of resolution upon antimalarial treatment, as survival was significantly decreased in the absence of NK cells. Considerably increased IL-10 expression by NK cells suggested an anti-inflammatory and pro-resolving phenotype. Despite the increase in Il10 expression in the NK cells, inhibition of the IL-10/IL-10R axis using anti-IL10R antibodies had no effect on the resolution for MA-ARDS, suggesting that the pro-resolving effect of NK cells cannot solely be attributed to their IL-10 production. In conclusion, NK cells contribute to the resolution of experimental MA-ARDS.

    Keywords: Malaria, Inflammation, Resolution, Natural Killer cells, immunology, Parasitology French (France)

    Received: 16 May 2024; Accepted: 27 Aug 2024.

    Copyright: © 2024 Pollenus, Possemiers, Knoops, Prenen, Vandermosten, Pham, Buysrogge, Matthys and Van den Steen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Philippe E. Van den Steen, Laboratory of Immunoparasitology, Department of Microbiology, Immunology and Transplantation, Rega Institute of Medical Research, KU Leuven, Leuven, Belgium

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