Ex vivo functional immune alterations in ICU patients with Legionnaires’ disease, a proof-of-concept study

Abstract

Objectives

Legionnaires’ disease (LD), caused by Legionella pneumophila intracellular bacterium, leads to intensive care unit (ICU) admission in 20-40% of cases. While ICU-LD patients display lung injury or septic shock (SS), their functional immune response remains poorly understood. This proof-of-concept study assessed ex vivo immune gene expression in ICU-LD and non-ICU-LD patients.

Methods

Whole blood from ICU-LD (n = 6), non-ICU-LD (n = 8), LD-unrelated SS (n = 14) and healthy volunteers (HVs) (n = 9) was stimulated with lipopolysaccharide (LPS). Expression of 93 immune-related genes was quantified using nCounter (NanoString Technologies) and expressed relative to HVs. Functional enrichment analyses were performed using the STRING database.

Results

ICU-LD patients displayed a 1.6-fold higher number of less induced genes (35/93 vs 22/93) and lower gene expression (median log2(FC): −1.9 vs −1.2, P = 0.0011) than non-ICU-LD. Top five pathways identified as enriched in ICU-LD but not in non-ICU-LD patients were cellular response to LPS, regulation of IFN-β production, I-κB/NF-κB complex, IFN regulatory factor complex and TRAF6-mediated NF-κB activation.

Conclusion

Ex vivo immune gene expression alterations were found in LD patients, particularly in ICU-LD patients. ICU-LD patients displayed lower expression of genes involved in crucial pathways for Legionella replication control. These preliminary findings support further studies to evaluate the impact of LD patients’ immune response on disease severity.