Detection of a TLR2 agonist by hematopoietic stem and progenitor cells impacts the function of the macrophages they produce.

TitleDetection of a TLR2 agonist by hematopoietic stem and progenitor cells impacts the function of the macrophages they produce.
Publication TypeJournal Article
Year of Publication2013
AuthorsYáñez A, Hassanzadeh-Kiabi N, Ng MY, Megías J, Subramanian A, Liu GY, Underhill DM, Gil LM, Goodridge HS
JournalEuropean journal of immunology
Volume43
Issue8
Pagination2114-25
Date Published2013 Aug
Abstract

Several groups have shown that detection of microbial components by TLRs on hematopoietic stem and progenitor cells (HSPCs) instructs myeloid cell generation, raising interest in the possibility of targeting TLRs on HSPCs 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 TLR2 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 TLR2 agonist ("tolerance"), which suppresses inflammatory cytokine production, but elevates reactive oxygen species. Soluble factors produced following exposure of HSPCs to a TLR2 agonist can also act in a paracrine manner to influence the function of macrophages derived from unexposed HSPCs. Our data demonstrate that macrophage function can be influenced by TLR signaling in the HSPCs from which they are derived, and that this may impact the clinical utility of targeting TLRs on HSPCs to boost myelopoiesis.

DOI10.3980/j.issn.2222-3959.2013.03.08
Alternate JournalEur. J. Immunol.