# Platelet–Neutrophil interactions in Klebsiella pneumoniae invasive syndrome: The role of aspirin

## TL;DR

This study explores how aspirin may help reduce complications in a severe bacterial infection linked to diabetes by affecting platelet and neutrophil interactions.

## Contribution

The study reveals aspirin's potential as an adjunct therapy in Klebsiella pneumoniae invasive syndrome by modulating platelet–neutrophil interactions under hyperglycemic conditions.

## Key findings

- High glucose levels increase platelet activation and bacterial survival in Klebsiella pneumoniae infections.
- Aspirin improves survival and reduces abscesses in diabetic mice infected with hypervirulent K. pneumoniae.
- Salicylic acid reduces platelet activation but does not prevent platelet–neutrophil aggregate formation.

## Abstract

Klebsiella pneumoniae invasive syndrome (KPIS), often arising from pyogenic liver abscesses, is characterized by metastatic infections and thrombotic complications. Diabetes mellitus (DM) is the most important risk factor for KPIS, as hyperglycemia promotes resistance of hypervirulent K. pneumoniae ;(hvKp) strains to phagocytosis and impairs neutrophil function. Given the interplay between platelet activation, inflammation, and thrombosis, aspirin, a well-established antiplatelet agent, has been associated with reduced incidence and recurrence of pyogenic liver abscesses in cohort studies. Platelets interact with neutrophils to form platelet – neutrophil aggregates (PNAs), which may contribute to KPIS pathogenesis. This study examined platelet – neutrophil interactions under hyperglycemic conditions using in vitro assays and in vivo models of diabetic mice infected with hvKp. High glucose concentrations significantly increased platelet activation, PNA formation, and bacterial survival. Salicylic acid, the bioactive metabolite of aspirin, reduced platelet activation and bacterial burden but did not impede PNA formation. Aspirin pre-treatment improved survival, reduced organ abscesses, and preserved tissue integrity in diabetic mice infected with hvKp. These results highlight the relationship between hyperglycemia, platelet activation, and immune dysregulation in KPIS, and support aspirin as a potential adjunctive therapy to mitigate thromboinflammatory complications of hvKp infection.