Streptococcus pneumoniae drives specific and lasting Natural Killer cell memory

PLoS Pathog. 2023 Jul 24;19(7):e1011159. doi: 10.1371/journal.ppat.1011159. eCollection 2023 Jul.

Abstract

NK cells are important mediators of innate immunity and play an essential role for host protection against infection, although their responses to bacteria are poorly understood. Recently NK cells were shown to display memory properties, as characterized by an epigenetic signature leading to a stronger secondary response. Although NK cell memory could be a promising mechanism to fight against infection, it has not been described upon bacterial infection. Using a mouse model, we reveal that NK cells develop specific and long-term memory following sub-lethal infection with the extracellular pathogen Streptococcus pneumoniae. Memory NK cells display intrinsic sensing and response to bacteria in vitro, in a manner that is enhanced post-bacterial infection. In addition, their transfer into naïve mice confers protection from lethal infection for at least 12 weeks. Interestingly, NK cells display enhanced cytotoxic molecule production upon secondary stimulation and their protective role is dependent on Perforin and independent of IFNγ. Thus, our study identifies a new role for NK cells during bacterial infection, opening the possibility to harness innate immune memory for therapeutic purposes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Immunity, Innate
  • Killer Cells, Natural*
  • Perforin
  • Streptococcus pneumoniae*

Substances

  • Perforin

Grants and funding

This study and M.A.H were supported by Institut Pasteur, the Agence Nationale de la Recherche (ANR-17-CE12-0007), the Fondation pour la Recherche Médicale (EQU202003010152), the Fondation iXCore-iXLife, the Don Prix CANETTI 2020, the EMBO Young Investigator Program. M.A.H is a member of the Laboratoire d’Excellence “Integrative Biology of Emerging Infectious Diseases” Agence Nationale de la Recherche (ANR): ANR-10-LABX- 62-EIBID). T.M.N.C received a salary from the Crédit Agricole d’Ile de France and Fondation pour la Recherche Médicale, grants no. PMJ201810007628 (Prix MARIANE JOSSO) and no. FDT202106012790 (Fin de thèse). J.T received a salary from the Fondation ARC, grant no. ARCPOST-DOC2021070004074. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.