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Detection of a TLR 2 agonist by hematopoietic stem and progenitor cells impacts the function of the macrophages they produce
Author(s) -
Yáñez Alberto,
HassanzadehKiabi Nargess,
Ng Madelena Y.,
Megías Javier,
Subramanian Aparna,
Liu George Y.,
Underhill David M.,
Gil M. Luisa,
Goodridge Helen S.
Publication year - 2013
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201343403
Subject(s) - myelopoiesis , haematopoiesis , biology , microbiology and biotechnology , progenitor cell , immunology , myeloid , macrophage , tlr2 , cytokine , stem cell , innate immune system , in vitro , immune system , biochemistry
Several groups have shown that detection of microbial components by TLR s on hematopoietic stem and progenitor cells ( HSPC s) instructs myeloid cell generation, raising interest in the possibility of targeting TLR s on HSPC s to boost myelopoiesis. However, although “ TLR ‐derived” cells exhibit myeloid cell characteristics (phagocytosis, cytokine production, antigen presentation), it is not clear whether they are functionally equivalent to macrophages derived in the absence of TLR activation. Our in vitro and in vivo studies show that macrophages derived from mouse and human HSPC subsets (including stem cells) exposed to a TLR 2 agonist prior to or during macrophage differentiation produce lower levels of inflammatory cytokines ( TNF ‐α, IL ‐6, and IL ‐1β) and reactive oxygen species. This is in contrast to prior exposure of differentiated macrophages to the TLR 2 agonist (“tolerance”), which suppresses inflammatory cytokine production, but elevates reactive oxygen species. Soluble factors produced following exposure of HSPC s to a TLR 2 agonist can also act in a paracrine manner to influence the function of macrophages derived from unexposed HSPC s. Our data demonstrate that macrophage function can be influenced by TLR signaling in the HSPC s from which they are derived, and that this may impact the clinical utility of targeting TLR s on HSPC s to boost myelopoiesis.