Impact of human monocyte and macrophage polarization on NLR expression and NLRP3 inflammasome activation
Impact of human monocyte and macrophage polarization on NLR expression and NLRP3 inflammasome activation
Date
2017-04-12
Authors
Awad, Fawaz
Assrawi, Eman
Jumeau, Claire
Georgin-Lavialle, Sophie
Cobret, Laetitia
Duquesnoy, Philippe
Piterboth, William
Thomas, Lucie
Stankovic-Stojanovic, Katia
Louvrier, Camille
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Abstract
Inflammasomes are multiprotein complexes nucleating around an NLR (Nucleotide-binding
domain and Leucine-rich Repeat containing protein), which regulate the secretion of the
pro-inflammatory interleukin (IL)-1β and IL-18 cytokines. Monocytes and macrophages, the
main cells expressing the inflammasome genes, adapt to their surrounding microenvironment
by a phenotypic polarization towards a pro-inflammatory M1 phenotype that promotes
inflammation or an anti-inflammatory M2 phenotype important for resolution of inflammation.
Despite the importance of inflammasomes in health and disease, little is known about
inflammasome gene expression in relevant human cells and the impact of monocyte and
macrophage polarization in inflammasome gene expression. We examined the expression
of several members of the NLR, caspase and cytokine family, and we studied the activation
of the well-described NLRP3 inflammasome in an experimental model of polarized human
primary monocytes and monocyte-derived macrophages (M1/M2 phenotypes) before and
after activation with LPS, a well-characterized microbial pattern used in inflammasome activation
studies. Our results show that the differentiation of monocytes to macrophages alters
NLR expression. Polarization using IFN-γ (M1 phenotype), induces among the NLRs studied,
only the expression of NOD2. One of the key results of our study is that the induction of
NLRP3 expression by LPS is inhibited in the presence of IL-4+IL-13 (M2 phenotype) at both
mRNA and protein level in monocytes and macrophages. Unlike caspase-3, the expression
of inflammasome-related CASP1 (encodes caspase-1) and CASP4 (encodes caspase-4) is
up-regulated in M1 but not in M2 cells. Interestingly, the presence of LPS marginally influenced
IL18 mRNA expression and secretion, unlike its impact on IL1B. Our data provide the
basis for a better understanding of the role of different inflammasomes within a given environment
(M1 and M2) in human cells and their impact in the pathophysiology of several
important inflammatory disorders.
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Citation
Awad F, Assrawi E, Jumeau C, Georgin- Lavialle S, Cobret L, Duquesnoy P, et al. (2017) Impact of human monocyte and macrophage polarization on NLR expression and NLRP3 inflammasome activation. PLoS ONE 12(4): e0175336