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Neutrophils Expressing Programmed Death-Ligand 1 Play an Indispensable Role in Effective Bacterial Elimination and Resolving Inflammation in Methicillin-Resistant Staphylococcus aureus Infection
Terasaki, A.; Ahmed, F.; Okuno, A.; Peng, Z.; Cao, D.-Y.; Saito, S. Neutrophils Expressing Programmed Death-Ligand 1 Play an Indispensable Role in Effective Bacterial Elimination and Resolving Inflammation in Methicillin-Resistant Staphylococcus aureus Infection. Pathogens2024, 13, 401.
Terasaki, A.; Ahmed, F.; Okuno, A.; Peng, Z.; Cao, D.-Y.; Saito, S. Neutrophils Expressing Programmed Death-Ligand 1 Play an Indispensable Role in Effective Bacterial Elimination and Resolving Inflammation in Methicillin-Resistant Staphylococcus aureus Infection. Pathogens 2024, 13, 401.
Terasaki, A.; Ahmed, F.; Okuno, A.; Peng, Z.; Cao, D.-Y.; Saito, S. Neutrophils Expressing Programmed Death-Ligand 1 Play an Indispensable Role in Effective Bacterial Elimination and Resolving Inflammation in Methicillin-Resistant Staphylococcus aureus Infection. Pathogens2024, 13, 401.
Terasaki, A.; Ahmed, F.; Okuno, A.; Peng, Z.; Cao, D.-Y.; Saito, S. Neutrophils Expressing Programmed Death-Ligand 1 Play an Indispensable Role in Effective Bacterial Elimination and Resolving Inflammation in Methicillin-Resistant Staphylococcus aureus Infection. Pathogens 2024, 13, 401.
Abstract
Programmed death ligand 1 (PD-L1) is a co-inhibitory molecule expressed on the surface of various
cell types, known for its suppressive effect on T cells through interaction with PD-1. Neutrophils also express
PD-L1, and its expression is elevated in specific situations; however, the immunobiological role of PD-L1+
neutrophil has not been fully characterized. Here, we report that PD-L1-expressing neutrophils increased in
methicillin-resistant Staphylococcus aureus (MRSA) infection are highly functional in bacterial elimination and
supporting inflammatory resolution. The frequency of PD-L1+ neutrophils was dramatically increased in
MRSA-infected mice, and this population exhibited enhanced activity in bacterial elimination compared to
PD-L1- neutrophils. An administration of PD-L1 monoclonal antibody did not impair PD-L1+ neutrophil
function suggesting that PD-L1 expression itself does not influence neutrophil activity. However, PD-1/PD-L1 blockade significantly delayed liver inflammation resolution in MRSA-infected mice, as indicated by increased plasma alanine transaminase (ALT) level and frequencies of inflammatory leukocytes in the liver implying that neutrophil PD-L1 suppresses the inflammatory response of these cells during the acute phase of MRSA infection. Our results reveal that elevated PD-L1 expression can be a marker for enhanced anti-bacterial function of neutrophils. Moreover, PD-L1+ neutrophils are an indispensable population attenuating inflammatory leukocyte activities assisting in a smooth transition into the resolution phase in MRSA infection.
Keywords
PD-L1, neutrophil, MRSA, PD-1, immunosuppressive
Subject
Biology and Life Sciences, Immunology and Microbiology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.