@Article{ecn.2017.0398,
AUTHOR = {Alba Martínez, Cristina Bono, Javier Megías, Alberto Yánez˜, Daniel Gozalbo, M. Luisa Gil},
TITLE = {PRR signaling during <i>in vitro</i> macrophage differentiation from progenitors modulates their subsequent response to inflammatory stimuli},
JOURNAL = {European Cytokine Network},
VOLUME = {28},
YEAR = {2017},
NUMBER = {3},
PAGES = {102--110},
URL = {http://www.techscience.com/ECN/v28n3/65515},
ISSN = {1952-4005},
ABSTRACT = {Toll-like receptor (TLR) agonists drive hematopoietic stem and progenitor cells (HSPCs) to differentiate
along the myeloid lineage <i>in vitro</i> and also<i> in vivo</i> following infection. In this study, we used an <i>in vitro</i> model
of HSPC differentiation to investigate the functional consequences (cytokine production) that exposing HSPCs
to various pathogen-associated molecular patterns (PAMPs) and <i>Candida albicans</i> cells have on the subsequently
derived macrophages. Mouse HSPCs (Lin– cells) were cultured with GM-CSF to induce macrophage differentiation
in the presence or absence of the following pattern recognition receptor (PRR) agonists: Pam<sub>3</sub>CSK<sub>4</sub> (TLR2
ligand), LPS (TLR4 ligand), depleted zymosan (which only activates Dectin-1), or inactivated <i>C. albicans</i> yeasts
(which activate several PRRs, mainly TLR2 and Dectin-1). Our data show that only pure TLR2 ligand exposure
(transient and continuous) impacts the inflammatory function of GM-CSF-derived macrophages, because
Pam<sub>3</sub>CSK<sub>4</sub>-exposed HSPCs generate macrophages with a diminished ability to produce inflammatory cytokines.
Interestingly, the Pam<sub>3</sub>CSK<sub>4</sub>-induced tolerance of macrophages (by transient exposure of HSPCs) is reinforced
by subsequent exposure to <i>C. albicans</i> cells in GM-CSF-derived macrophages; however, the induced tolerance is
partially reversed in M-CSF-derived macrophages. Therefore, the ability of macrophages to produce inflammatory
cytokines is extremely dependent on how the HSPCs from which they are derived receive and integrate multiple
microenvironmental signals (PRR ligands and/or CSFs).},
DOI = {10.1684/ecn.2017.0398}
}