Toll-like receptor expression on young and old hematopoietic cell types

Abstract

Abstract Hematopoiesis is an essential process that produces white and red blood cells within the body. As the body ages, we have observed defects in the hematopoietic process including an increase in the number of stem cells, skewing of white blood cells down the myeloid lineage, and a decrease in the production of new B and T cells. Since hematopoietic aging skews the production of professional immune cells, the elderly population has a disadvantage in recognizing and clearing infections compared to young individuals. Immune cells use a common bacterial and viral recognition system, which includes toll-like receptors (TLRs), to identify common pathogen-associated molecular patterns (PAMPs) that bacteria and viruses produce. Upon exposure, immune cells will activate to complete two functions: to direct myeloid differentiation for acute responses and to recognize and eliminate the pathogens via the TNFα or type 1 interferon (IFN-1) signaling pathway. Deficiencies in aging hematopoiesis, IFN-1 expression, and the TLR responses associated with IFN-1 in immune cells have been described in both mice and humans. The expression of these TLRs and any age-associated changes in that expression, as well as downstream signaling, are not as well established. Our goal is to identify which hematopoietic cells express the four TLRs associated with IFN-1 (TLR-3, −4, −7, −9) and if aging leads to changes in receptor expression and/or downstream signaling in human immune cells. Using flow cytometry, we evaluated receptor expression and the downstream effects of TLR engagement. The data reveals age-associated changes in IFN-1-related innate immune signaling pathways. Supported by grants from NIH (R00 AG055717)