# Activation of Natural Killer Cells in Patients with Chronic Bone and Joint Infection due to Staphylococci Expressing or Not the Small Colony Variant Phenotype

## TL;DR

This study found that NK cells are activated in patients with chronic bone and joint infections, regardless of whether the bacteria express a specific variant called SCV.

## Contribution

The study reveals that NK cell activation occurs universally in chronic BJI patients, independent of the SCV phenotype.

## Key findings

- NK cells showed activation markers like CD69, loss of CD16, and perforin in all infected patients.
- Degranulation occurred in response to CD16-mediated signals in chronic BJI patients.
- The findings suggest that chronic BJI bacteria may produce undetectable SCVs in vivo.

## Abstract

Chronic bone and joint infections (BJI) are devastating diseases. Relapses are frequently observed, as some pathogens, especially staphylococci, can persist intracellularly by expressing a particular phenotype called small colony variant (SCV). As natural killer (NK) cells are lymphocytes specialized in the killing of host cells infected by intracellular pathogens, we studied NK cells of patients with chronic BJI due to staphylococci expressing or not SCVs (10 patients in both groups). Controls were patients infected with other bacteria without detectable expression of SCVs, and healthy volunteers. NK cell phenotype was evaluated from PBMCs by flow cytometry. Degranulation capacity was evaluated after stimulation with K562 cells in vitro. We found that NK cells were activated in terms of CD69 expression, loss of CD16 and perforin, in all infected patients in comparison with healthy volunteers, independently of the SCV phenotype. Peripheral NK cells in patients with chronic BJI display signs of recent activation and degranulation in vivo in response to CD16-mediated signals, regardless of the type of bacteria involved. This could involve a universal capacity of isolates responsible for chronic BJI to produce undetectable SCVs in vivo, which might be a target of future intervention.