Functional alterations of immune gene expression in ICU and non-ICU patients with Legionnaires' disease, a prospective observational study

Allam, C.; Mouton, W.; Albert-Vega, C.; Ibranosyan, M.; Ginevra, C.; Descours, G.; Beraud, L.; Chapalain, A.; Zoued, A.; Argaud, L.; Friggeri, A.; Labeye, V.; Jamilloux, Y.; Lukaszewicz, A.-C.; Monneret, G.; Lopez, J.; Freymond, N.; Lina, G.; Doublet, P.; Richard, J. C.; Venet, F.; Ader, F.; Trouillet-Assant, S.; Jarraud, S.

doi:10.64898/2026.03.06.709905

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bioRxiv · 10.64898/2026.03.06.709905

Functional alterations of immune gene expression in ICU and non-ICU patients with Legionnaires' disease, a prospective observational study

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Abstract

Legionnaires disease (LD), a pneumonia caused by Legionella pneumophila intracellular bacterium, leads to intensive care unit (ICU) admission in 20-40% of cases. While these ICU-LD patients display severe lung injury or septic shock, their functional immune response remains poorly understood. The present study aimed, through a large immune gene expression assessment, to improve the understanding of immune cell functionality after whole blood LPS ex vivo stimulation in ICU-LD patients compared with non-ICU. Both ICU and non-ICU-LD displayed altered gene expression indicating that both patients immune cells are less able to respond to the LPS ex vivo stimulus than a healthy population. ICU-LD patients had 1.6-fold greater number of less-expressed genes (35/93 vs 22/93, p=0.039), and lower Log2(FC) of these genes (median [IQR]: -1.9 [-2.6;-1.5] vs -1.2 [-1.7;-0.9], p=0.0011) than non-ICU-LD. Seven genes were significantly less expressed by ICU-LD patients (IRF7, MX1, NFKBI2, NFKBIA, RELB, SRC, TIM3; p-value range: 0.029-0.0080). Top five gene ontology biological processes, subcellular localisations, and reactome pathways (STRING database) uniquely enriched in ICU-LD-patients and related less-expressed genes were cellular response to LPS (CCL2, NFKBIA, IRAK2, TIM3, SRC, NFKB1), regulation of IFN-{beta} production (IRF7, RIG1, OAS2, RELB), I-{kappa}B/NF-{kappa}B complex (NFKBIA, NFKB1, NFKB2), IFN regulatory factor complex (RIG1, IRF7), and TRAF6-mediated NF-{kappa}B activation pathway (NFKBIA, NFKB1, NFKB2, RIG1). Immune gene expression alterations in LD after LPS stimulation were found herein, with more pronounced alterations in ICU-LD patients. A reduced expression of key genes and pathways involved in controlling Legionella proliferation in ICU-LD patients may contribute to increased disease severity.

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Allam, C., Mouton, W., Albert-Vega, C., Ibranosyan, M., Ginevra, C., Descours, G., Beraud, L., Chapalain, A., Zoued, A., Argaud, L., Friggeri, A., Labeye, V., Jamilloux, Y., Lukaszewicz, A.-C., Monneret, G., Lopez, J., Freymond, N., Lina, G., Doublet, P., Richard, J. C., Venet, F., Ader, F., Trouillet-Assant, S., Jarraud, S.. 2026-03-09. Functional alterations of immune gene expression in ICU and non-ICU patients with Legionnaires' disease, a prospective observational study. https://doi.org/10.64898/2026.03.06.709905

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