International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2026
Ex vivo functional immune alterations in ICU patients with Legionnaires' Disease, a proof-of-concept study.
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Allam Camille, Mouton William, Albert-Vega Chloé, Ibranosyan Marine, Ginevra Christophe, Descours Ghislaine, Beraud Laetitia, Chapalain Annelise, Zoued Abdelrahim, Argaud Laurent, Friggeri Arnaud, Labeye Vanessa, Jamilloux Yvan, Lukaszewicz Anne-Claire, Monneret Guillaume, Lopez Jonathan, Freymond Nathalie, Lina Gerard, Doublet Patricia, Richard Jean-Christophe, Venet Fabienne, Ader Florence, Trouillet-Assant Sophie, Jarraud Sophie
Аннотация
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, 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 septic shock (n=14), and healthy volunteers (n=9) was stimulated with lipopolysaccharide (LPS). Expression of 93 immune-related genes was quantified using nCounter (NanoString Technologies) and expressed relative to healthy volunteers. 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.
CONCLUSIONS: 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.
METHODS: Whole blood from ICU-LD (n=6), non-ICU-LD (n=8), LD-unrelated septic shock (n=14), and healthy volunteers (n=9) was stimulated with lipopolysaccharide (LPS). Expression of 93 immune-related genes was quantified using nCounter (NanoString Technologies) and expressed relative to healthy volunteers. 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.
CONCLUSIONS: 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.