Objectives The lung disease progression in people with cystic fibrosis (pwCF) varies from one individual to another. Different immunological characteristics have been suggested to explain this variation, and we hypothesized that lung capacity may be associated with the innate immune response in pwCF. In an exploratory study, we aimed to investigate potential links between the innate immune response and lung function in pwCF using the standardized immune function assay TruCulture. Methods In a single-centre study with combined cross-sectional and longitudinal data before and after intravenous antibiotics, blood was sampled from Pseudomonas aeruginosa infected pwCF. Whole blood was analysed by TruCulture to reveal the unstimulated and stimulated cytokine release. Tobit regressions and Spearman's correlations were used to estimate the associations between lung function and cytokine release. Results We included 52 pwCF in the cross-sectional study and 24 in the longitudinal study. In the cross-sectional study, we found that compared to a healthy population the release of toll-like receptor (TLR)3, −4 and −7/8 stimulated IFN-γ, and IL-12p40 were reduced. Although TLR3-stimulated IL-1β and IL-6 release increased with lung function, overall, cytokine release did not correlate well with lung function. In the longitudinal study, the cytokine release was modified by antibiotic treatment, but the cytokine release before antibiotic treatment did not associate with changes in lung function after treatment. Conclusion The stimulated cytokine release could not predict lung function levels or changes in pwCF, but our data indicate that pwCF experience exhaustion in the innate immune response after years of chronic bacterial infection.

Clinical implications of innate immune exhaustion in cystic fibrosis / R. Møller, B. Uhre Nielsen, E. Rossi, M. Lausen, M. Skov, T. Pressler, S. Rye Ostrowski, H. Krogh Johansen. - In: ERJ OPEN RESEARCH. - ISSN 2312-0541. - 10:2(2024 Apr), pp. 1-22. [10.1183/23120541.00256-2024]

Clinical implications of innate immune exhaustion in cystic fibrosis

E. Rossi
Secondo
;
2024

Abstract

Objectives The lung disease progression in people with cystic fibrosis (pwCF) varies from one individual to another. Different immunological characteristics have been suggested to explain this variation, and we hypothesized that lung capacity may be associated with the innate immune response in pwCF. In an exploratory study, we aimed to investigate potential links between the innate immune response and lung function in pwCF using the standardized immune function assay TruCulture. Methods In a single-centre study with combined cross-sectional and longitudinal data before and after intravenous antibiotics, blood was sampled from Pseudomonas aeruginosa infected pwCF. Whole blood was analysed by TruCulture to reveal the unstimulated and stimulated cytokine release. Tobit regressions and Spearman's correlations were used to estimate the associations between lung function and cytokine release. Results We included 52 pwCF in the cross-sectional study and 24 in the longitudinal study. In the cross-sectional study, we found that compared to a healthy population the release of toll-like receptor (TLR)3, −4 and −7/8 stimulated IFN-γ, and IL-12p40 were reduced. Although TLR3-stimulated IL-1β and IL-6 release increased with lung function, overall, cytokine release did not correlate well with lung function. In the longitudinal study, the cytokine release was modified by antibiotic treatment, but the cytokine release before antibiotic treatment did not associate with changes in lung function after treatment. Conclusion The stimulated cytokine release could not predict lung function levels or changes in pwCF, but our data indicate that pwCF experience exhaustion in the innate immune response after years of chronic bacterial infection.
Settore BIO/19 - Microbiologia Generale
Settore MED/07 - Microbiologia e Microbiologia Clinica
Settore MED/04 - Patologia Generale
Settore MED/05 - Patologia Clinica
   BacVir-CF: identification of novel bacterial virulence factors and inflammation determinants associated with persistent lung infection in cystic fibrosis
   FONDAZIONE CARIPLO
   2020-3581
apr-2024
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1047430
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