Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Gram-Positive Staphylococcus aureus LTA Promotes Distinct Memory-like Effects in Murine Bone Marrow Neutrophils

Version 1 : Received: 15 November 2021 / Approved: 1 December 2021 / Online: 1 December 2021 (11:00:01 CET)

A peer-reviewed article of this Preprint also exists.

Journal reference: Cellular Immunology 2022
DOI: 10.1016/j.cellimm.2022.104535

Abstract

Neutrophils as innate immune cells primarily act as first responders in acute infection and directly maintain inflammatory responses. However, a growing body of evidence suggests that neutrophils also bear the potential to mediate chronic inflammation by exhibiting memory-like features. We recently showed that priming by serial doses of lipopolysaccharide (LPS) from gram-negative bacteria can trigger opposing memory-like responses (exaggerated inflammation, i.e. trained sensitivity or suppression of inflammation, i.e. tolerance) depending on the LPS-dose. We now asked whether this observation could also hold true for lipoteichoic acid (LTA) from gram-positive S. aureus. We found comparable effects of LTA on neutrophil priming as seen for LPS. Low-dose (1 ng/mL) LTA-priming promoted increased production of pro-inflammatory mediators (i.e., TNF-α, IL-6, ROS), whereas high-dose (10 µg/mL) results in contrary reactions supporting anti-inflammatory responses by increased IL-10 and declined pro-inflammatory capacity. In vitro neutrophil recruitment was similarly regulated by LTA -priming. Investigation of signalling patterns revealed TLR2/MyD88-mediated regulation of NFκB-p65 through intermediate PI3Ks/MAPK. Collectively, our data suggest a previously unknown capacity of neutrophils to be differentially primed by varying doses of LTA, endorsing memory-like features in neutrophils.

Keywords

neutrophils; priming; innate immunity; immune-memory

Subject

MEDICINE & PHARMACOLOGY, Other

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