Dectin-1 signaling in neutrophils up-regulates PD-L1 and triggers ROS-mediated suppression of CD4+ T cells

Author:

Deerhake M Elizabeth1ORCID,Cardakli Emre D12,Shinohara Mari L13

Affiliation:

1. Department of Immunology, Duke University School of Medicine , Durham, North Carolina, USA

2. Tri-Institutional MD-PhD Program, Weill Cornell Medical College, Rockefeller University and Memorial Sloan Kettering Cancer Center , New York, New York, USA

3. Department of Molecular Genetics and Microbiology, Duke University School of Medicine , Durham, North Carolina, USA

Abstract

Abstract Dectin-1 is known to drive proinflammatory cytokine production by macrophages and dendritic cells which promotes Th17 CD4+ T cell responses in the setting of fungal infection. However, the role of Dectin-1 signaling in neutrophils and its impact on CD4+ T cells is not well understood. In this study, we found that neutrophils stimulated with a Dectin-1 agonist diminish CD4+ T cell viability in a rapid and reactive oxygen species (ROS)-dependent manner. Furthermore, Dectin-1 promoted neutrophil PD-L1 expression via Syk and Card9 signaling, along with other immune-checkpoint factors in a neutrophil-biased manner. Although neutrophil PD-L1 did not significantly impact disease severity in experimental autoimmune encephalomyelitis (EAE), we found that CNS-infiltrated neutrophils potently up-regulate PD-L1 expression. Furthermore, a subset of PD-L1+ neutrophils was also found to express MHC-II during EAE. In summary, we found that Dectin-1 elicits a biphasic neutrophil response in which (1) T-cell suppressive ROS is followed by (2) up-regulation of PD-L1 expression. This response may serve to limit excess CD4+ T cell-driven inflammation in infection or autoimmunity while preserving host-defense functions of neutrophils. Summary sentence: Mechanisms by which Dectin-1 signaling in neutrophils promotes a cellular phenotype with T cell-suppressive properties.

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Immunology,Immunology and Allergy

Reference43 articles.

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