PD-1 Expression on NK Cells in Malaria-Exposed Individuals Is Associated with Diminished Natural Cytotoxicity and Enhanced Antibody-Dependent Cellular Cytotoxicity.

Abstract

Natural killer (NK) cells are key effector cells of innate resistance capable of destroying tumors and virus-infected cells through cytotoxicity and rapid cytokine production. The control of NK cell responses is complex and only partially understood. PD-1 is an inhibitory receptor that regulates T cell function, but a role for PD-1 in regulating NK cell function is only beginning to emerge. Here, we investigated PD-1 expression on NK cells in children and adults in Mali in a longitudinal analysis before, during, and after infection with Plasmodium falciparum malaria. We found that NK cells transiently upregulate PD-1 expression and interleukin-6 (IL-6) production in some individuals during acute febrile malaria. Furthermore, the percentage of PD-1 expressing NK cells increases with age and cumulative malaria exposure. Consistent with this, NK cells of malaria-naive adults upregulated PD-1 following P. falciparum stimulation in vitro Additionally, functional in vitro studies revealed that PD-1 expression on NK cells is associated with diminished natural cytotoxicity but enhanced antibody-dependent cellular cytotoxicity (ADCC). These data indicate that PD-1+ NK cells expand in the context of chronic immune activation and suggest that PD-1 may contribute to skewing NK cells toward enhanced ADCC during infections such as malaria.

• Authors: Jacqueline Moebius, Rajan Guha, Mary Peterson, Kaveh Abdi, Jeff Skinner, Shanping Li, Gunjan Arora, Boubacar Traore, Sumati Rajagopalan, Eric O Long, Peter D Crompton
• Journal: Infection and immunity (Infect Immun) Vol. 88 Issue 3 (02 20 2020) ISSN: 1098-5522 [Electronic] United States
• PMID: 31907195 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
• Copyright: Copyright © 2020 American Society for Microbiology.

Chemical References

• CD56 Antigen
• FCGR3B protein, human
• GPI-Linked Proteins
• IL6 protein, human
• Interleukin-6
• NCAM1 protein, human
• PDCD1 protein, human
• Programmed Cell Death 1 Receptor
• Receptors, IgG

Topics

• Adult
• Age Factors
• Animals
• Antibody-Dependent Cell Cytotoxicity
• CD56 Antigen (metabolism)
• Cell Line
• Child
• GPI-Linked Proteins (metabolism)
• Humans
• Interleukin-6 (metabolism)
• K562 Cells
• Killer Cells, Natural (immunology)
• Longitudinal Studies
• Malaria (immunology)
• Malaria, Falciparum (immunology)
• Mice
• Plasmodium falciparum (pathogenicity)
• Programmed Cell Death 1 Receptor (metabolism)
• Receptors, IgG (metabolism)