Serum inflammatory profiles in cystic fibrosis mice with and without Bordetella pseudohinzii infection

Abstract Cystic fibrosis (CF) is an autosomal recessive disease caused by dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) protein, and is marked by an accumulation of mucus in affected airways resulting in persistent infection and chronic inflammation. Quantitative differenc...

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Autores principales:	Paul M. Litman, Alexander Day, Thomas J. Kelley, Rebecca J. Darrah
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/31f0874a7c12440ebf4474eafd49f997
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spelling	oai:doaj.org-article:31f0874a7c12440ebf4474eafd49f9972021-12-02T19:04:11ZSerum inflammatory profiles in cystic fibrosis mice with and without Bordetella pseudohinzii infection10.1038/s41598-021-97033-92045-2322https://doaj.org/article/31f0874a7c12440ebf4474eafd49f9972021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97033-9https://doaj.org/toc/2045-2322Abstract Cystic fibrosis (CF) is an autosomal recessive disease caused by dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) protein, and is marked by an accumulation of mucus in affected airways resulting in persistent infection and chronic inflammation. Quantitative differences in inflammatory markers have been observed in CF patient serum, tracheal cells, and bronchoalveolar lavage fluid, in the absence of detectable infection, implying that absent CFTR function alone may result in dysregulated immune responses. To examine the relationship between absent CFTR and systemic inflammation, 22 analytes were measured in CF mice (F508del/F508del) sera using the MSD multiplex platform. Pro-inflammatory cytokines IL-2, TNF-α, IL-17α, IFN-γ, IL-1β, and MIP-3α are significantly elevated in infection-naïve CF mice (p < 0.050). Anti-inflammatory cytokines IL-10 and IL-4 are also significantly increased (p = 0.00003, p = 0.004). Additionally, six general markers of inflammation are significantly different from non-CF controls (p < 0.050). To elucidate the effects of chronic infection on the CF inflammatory profile, we examined CF mice exposed to spontaneous Bordetella pseudohinzii infections. There are no statistical differences in nearly all inflammatory markers when compared to their infection-naïve CF counterparts, except in the Th2-derived IL-4 and IL-5 which demonstrate significant decreases following exposure (p = 0.046, p = 0.045). Lastly, following acute infection, CF mice demonstrate elevations in nearly all inflammatory markers, but exhibit a shortened return to uninfected levels over time, and suppression of Th1-derived IL-2 and IL-5 (p = 0.043, p = 0.011). These results imply that CF mice have a persistent inflammatory profile often indistinguishable from chronic infection, and a dysregulated humoral response during and following active infection.Paul M. LitmanAlexander DayThomas J. KelleyRebecca J. DarrahNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Paul M. Litman Alexander Day Thomas J. Kelley Rebecca J. Darrah Serum inflammatory profiles in cystic fibrosis mice with and without Bordetella pseudohinzii infection
description	Abstract Cystic fibrosis (CF) is an autosomal recessive disease caused by dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) protein, and is marked by an accumulation of mucus in affected airways resulting in persistent infection and chronic inflammation. Quantitative differences in inflammatory markers have been observed in CF patient serum, tracheal cells, and bronchoalveolar lavage fluid, in the absence of detectable infection, implying that absent CFTR function alone may result in dysregulated immune responses. To examine the relationship between absent CFTR and systemic inflammation, 22 analytes were measured in CF mice (F508del/F508del) sera using the MSD multiplex platform. Pro-inflammatory cytokines IL-2, TNF-α, IL-17α, IFN-γ, IL-1β, and MIP-3α are significantly elevated in infection-naïve CF mice (p < 0.050). Anti-inflammatory cytokines IL-10 and IL-4 are also significantly increased (p = 0.00003, p = 0.004). Additionally, six general markers of inflammation are significantly different from non-CF controls (p < 0.050). To elucidate the effects of chronic infection on the CF inflammatory profile, we examined CF mice exposed to spontaneous Bordetella pseudohinzii infections. There are no statistical differences in nearly all inflammatory markers when compared to their infection-naïve CF counterparts, except in the Th2-derived IL-4 and IL-5 which demonstrate significant decreases following exposure (p = 0.046, p = 0.045). Lastly, following acute infection, CF mice demonstrate elevations in nearly all inflammatory markers, but exhibit a shortened return to uninfected levels over time, and suppression of Th1-derived IL-2 and IL-5 (p = 0.043, p = 0.011). These results imply that CF mice have a persistent inflammatory profile often indistinguishable from chronic infection, and a dysregulated humoral response during and following active infection.
format	article
author	Paul M. Litman Alexander Day Thomas J. Kelley Rebecca J. Darrah
author_facet	Paul M. Litman Alexander Day Thomas J. Kelley Rebecca J. Darrah
author_sort	Paul M. Litman
title	Serum inflammatory profiles in cystic fibrosis mice with and without Bordetella pseudohinzii infection
title_short	Serum inflammatory profiles in cystic fibrosis mice with and without Bordetella pseudohinzii infection
title_full	Serum inflammatory profiles in cystic fibrosis mice with and without Bordetella pseudohinzii infection
title_fullStr	Serum inflammatory profiles in cystic fibrosis mice with and without Bordetella pseudohinzii infection
title_full_unstemmed	Serum inflammatory profiles in cystic fibrosis mice with and without Bordetella pseudohinzii infection
title_sort	serum inflammatory profiles in cystic fibrosis mice with and without bordetella pseudohinzii infection
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/31f0874a7c12440ebf4474eafd49f997
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Serum inflammatory profiles in cystic fibrosis mice with and without Bordetella pseudohinzii infection

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