TLRs control hematopoiesis during infection - PubMed (original) (raw)

Review

TLRs control hematopoiesis during infection

Alberto Yáñez et al. Eur J Immunol. 2013 Oct.

Abstract

Recent research has shown that (i) Toll-like receptor (TLR) agonists drive hematopoietic stem and progenitor cells (HSPCs) to proliferate and differentiate along the myeloid lineage in vitro, and (ii) direct TLR-mediated stimulation of HSPCs also promotes macrophage differentiation in vivo following infection. These new insights demonstrate that TLR signaling in HSPCs, in addition to other TLR-dependent mechanisms, can contribute to HSPC expansion and myeloid differentiation after infection. Evidence is, therefore, mounting that direct TLR-induced programming of hematopoiesis plays a key role in host defense by rapidly replenishing the innate immune system with the cells needed to deal with pathogens.

Keywords: Hematopoiesis; Hematopoietic stem and progenitor cells; Infection; TLRs.

© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest

The authors declare no financial or commercial conflict of interest.

Figures

Figure 1

Figure 1. The mouse hematopoietic tree

Hematopoiesis is initiated in the bone marrow by normally quiescent long-term hematopoietic stem cells (LT-HSCs), which have the capacity for self-renewal and give rise to proliferating short-term HSCs (ST-HSCs). ST-HSCs produce multipotent progenitors (MPPs), which give rise to progenitors committed to specific hematopoietic lineages, common lymphoid progenitors (CLPs) and common myeloid progenitors (CMPs). Mouse HSPCs from the bone marrow are defined by their lack of expression of markers of differentiated cells. A cocktail of antibodies specific for differentiated blood cell antigens, termed “lineage markers” (Lin; typically CD5, CD45R (B220), CD11b, Gr-1 (Ly-6G/C), 7–4, and Ter-119) can be used to eliminate mature hematopoietic lineages. The remaining Lin− cells can then be enriched for specific stem/progenitor populations. Sorting Lin− c-Kit+ Sca-1+ (LKS+) cells enriches for hematopoietic-reconstituting activity (i.e. HSCs). However, only 10% LKS+ cells are bona fide long-term reconstituting (LT)-HSCs; the LKS+ population also includes short-term (ST)-HSCs and MPPs. The Lin− c-Kit+ Sca-1− (LKS−) fraction contains oligopotent lineage-committed progenitors. CLPs generate all classes of lymphocytes, and CMPs give rise to either megakaryocyte-erythrocyte progenitors (MEPs) or granulocyte-monocyte progenitors (GMPs). Dendritic cell (DC) potential is retained in both CMPs and CLPs. In addition to producing GMPs, CMPs also give rise to monocyte and DC progenitors (MDPs), which can generate monocytes, macrophages, classical DCs (cDCs) and plasmacytoid DCs (pDCs). MDPs lie upstream of the common DC progenitors (CDPs), which are DC-restricted, giving rise to pDCs and cDCs. Monocytes can further differentiate into macrophages or monocyte-derived DCs (moDCs).

Figure 2

Figure 2. C. albicans directly stimulates HSPCs to induce myelopoiesis

C. albicans interacts in vitro with mouse HSPCs from the most quiescent HSCs (LT-HSCs) to the lineage-committed progenitors (CMPs and GMPs, top), inducing the differentiation of these cells towards the myeloid lineage in a TLR2-dependent manner. C. albicans also induces TLR2- and Dectin-1-dependent production of moDCs by Lin− HSPCs in vitro, and TLR2-dependent macrophage production by transplanted LKS+ and Lin− cells upon C. albicans infection in vivo (bottom). Dectin-1 activation also promotes monocyte differentiation to macrophages and moDCs (bottom).

Similar articles

Cited by

References

    1. Geissmann F, Manz MG, Jung S, Sieweke MH, Merad M, Ley K. Development of monocytes, macrophages, and dendritic cells. Science. 2010;327:656–661. - PMC - PubMed
    1. Schmid MA, Kingston D, Boddupalli S, Manz MG. Instructive cytokine signals in dendritic cell lineage commitment. Immunol Rev. 2010;234:32–44. - PubMed
    1. Iwasaki H, Akashi K. Myeloid lineage commitment from the hematopoietic stem cell. Immunity. 2007;26:726–740. - PubMed
    1. Jenkins SJ, Ruckerl D, Cook PC, Jones LH, Finkelman FD, van Rooijen N, MacDonald AS, Allen JE. Local macrophage proliferation, rather than recruitment from the blood, is a signature of TH2 inflammation. Science. 2011;332:1284–1288. - PMC - PubMed
    1. Baldridge MT, King KY, Goodell MA. Inflammatory signals regulate hematopoietic stem cells. Trends Immunol. 2011;32:57–65. - PMC - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources