Uncoupling between inflammatory and fibrotic responses to silica: evidence from MyD88 knockout mice.
The exact implication of innate immunity in granuloma formation and irreversible lung fibrosis remains to be determined. In this study, we examined the lung inflammatory and fibrotic responses to silica in MyD88-knockout (KO) mice. In comparison to wild-type (WT) mice, we found that MyD88-KO animals...
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doaj-3b7e99d74d1d4feea5543b76947177db2020-11-25T02:15:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0197e9938310.1371/journal.pone.0099383Uncoupling between inflammatory and fibrotic responses to silica: evidence from MyD88 knockout mice.Sandra Lo ReGiulia GiordanoYousof YakoubRaynal DevosseFrancine UwambayinemaIsabelle CouillinBernard RyffelEtienne MarbaixDominique LisonFrançois HuauxThe exact implication of innate immunity in granuloma formation and irreversible lung fibrosis remains to be determined. In this study, we examined the lung inflammatory and fibrotic responses to silica in MyD88-knockout (KO) mice. In comparison to wild-type (WT) mice, we found that MyD88-KO animals developed attenuated lung inflammation, neutrophil accumulation and IL-1β release in response to silica. Granuloma formation was also less pronounced in MyD88-KO mice after silica. This limited inflammatory response was not accompanied by a concomitant attenuation of lung collagen accumulation after silica. Histological analyses revealed that while pulmonary fibrosis was localized in granulomas in WT animals, it was diffusely distributed throughout the parenchyma in MyD88-KO mice. Robust collagen accumulation was also observed in mice KO for several other components of innate immunity (IL-1R, IL-1, ASC, NALP3, IL-18R, IL-33R, TRIF, and TLR2-3-4,). We additionally show that pulmonary fibrosis in MyD88-KO mice was associated with the accumulation of pro-fibrotic regulatory T lymphocytes (T regs) and pro-fibrotic cytokine expression (TGF-β, IL-10 and PDGF-B), not with T helper (Th) 17 cell influx. Our findings indicate that the activation of MyD88-related innate immunity is central in the establishment of particle-induced lung inflammatory and granuloma responses. The development of lung fibrosis appears uncoupled from inflammation and may be orchestrated by a T reg-associated pathway.http://europepmc.org/articles/PMC4106757?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sandra Lo Re Giulia Giordano Yousof Yakoub Raynal Devosse Francine Uwambayinema Isabelle Couillin Bernard Ryffel Etienne Marbaix Dominique Lison François Huaux |
spellingShingle |
Sandra Lo Re Giulia Giordano Yousof Yakoub Raynal Devosse Francine Uwambayinema Isabelle Couillin Bernard Ryffel Etienne Marbaix Dominique Lison François Huaux Uncoupling between inflammatory and fibrotic responses to silica: evidence from MyD88 knockout mice. PLoS ONE |
author_facet |
Sandra Lo Re Giulia Giordano Yousof Yakoub Raynal Devosse Francine Uwambayinema Isabelle Couillin Bernard Ryffel Etienne Marbaix Dominique Lison François Huaux |
author_sort |
Sandra Lo Re |
title |
Uncoupling between inflammatory and fibrotic responses to silica: evidence from MyD88 knockout mice. |
title_short |
Uncoupling between inflammatory and fibrotic responses to silica: evidence from MyD88 knockout mice. |
title_full |
Uncoupling between inflammatory and fibrotic responses to silica: evidence from MyD88 knockout mice. |
title_fullStr |
Uncoupling between inflammatory and fibrotic responses to silica: evidence from MyD88 knockout mice. |
title_full_unstemmed |
Uncoupling between inflammatory and fibrotic responses to silica: evidence from MyD88 knockout mice. |
title_sort |
uncoupling between inflammatory and fibrotic responses to silica: evidence from myd88 knockout mice. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
The exact implication of innate immunity in granuloma formation and irreversible lung fibrosis remains to be determined. In this study, we examined the lung inflammatory and fibrotic responses to silica in MyD88-knockout (KO) mice. In comparison to wild-type (WT) mice, we found that MyD88-KO animals developed attenuated lung inflammation, neutrophil accumulation and IL-1β release in response to silica. Granuloma formation was also less pronounced in MyD88-KO mice after silica. This limited inflammatory response was not accompanied by a concomitant attenuation of lung collagen accumulation after silica. Histological analyses revealed that while pulmonary fibrosis was localized in granulomas in WT animals, it was diffusely distributed throughout the parenchyma in MyD88-KO mice. Robust collagen accumulation was also observed in mice KO for several other components of innate immunity (IL-1R, IL-1, ASC, NALP3, IL-18R, IL-33R, TRIF, and TLR2-3-4,). We additionally show that pulmonary fibrosis in MyD88-KO mice was associated with the accumulation of pro-fibrotic regulatory T lymphocytes (T regs) and pro-fibrotic cytokine expression (TGF-β, IL-10 and PDGF-B), not with T helper (Th) 17 cell influx. Our findings indicate that the activation of MyD88-related innate immunity is central in the establishment of particle-induced lung inflammatory and granuloma responses. The development of lung fibrosis appears uncoupled from inflammation and may be orchestrated by a T reg-associated pathway. |
url |
http://europepmc.org/articles/PMC4106757?pdf=render |
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