Abstract
microRNAs (miRNAs) have emerged as important regulators of the innate and adaptive immune response. The purpose of the present study was to interrogate miRNA profiles of primary human macrophages challenged with bacterial lipopolysaccharide (LPS) with focus on expression kinetics. We employed Nanostring platform to precisely characterize the changes in miRNA expression following different doses and durations of LPS exposure. Differentially expressed miRNAs were identified in response to LPS challenge with convergent and divergent expression profiles. Pathway analysis of LPS-responsive miRNAs revealed regulation of biological processes linked to key cell signaling (including PIK3-Akt, MAP kinase, ErbB) and pathogen response pathways. Our data provide a comprehensive miRNA profiling of human primary macrophages treated with LPS. These results show that bacterial Toll like receptor (TLR) ligands can temporally modulate macrophage miRNA expression.
Highlights
The initial immune response to bacterial infection involves the recognition of conserved pathogen-associated molecular patterns (PAMPs) such as LPS, lipoteichoic acid and peptidoglycans by pathogen recognition receptors (PRRs) including toll-like receptors (TLRs), RIGI-like receptors and NOD-like receptors [1,2,3]
PRRs are expressed by a variety of cell types including macrophages (Mφ), dendritic cells (DC), epithelial cells, fibroblasts and neutrophils [1,4]
The innate immune response to PAMPs is associated with modulation of the host cell transcriptome
Summary
The initial immune response to bacterial infection involves the recognition of conserved pathogen-associated molecular patterns (PAMPs) such as LPS, lipoteichoic acid and peptidoglycans by pathogen recognition receptors (PRRs) including toll-like receptors (TLRs), RIGI-like receptors and NOD-like receptors [1,2,3]. PRRs are expressed by a variety of cell types including macrophages (Mφ), dendritic cells (DC), epithelial cells, fibroblasts and neutrophils [1,4]. Recognition of PAMPs initiates intracellular signaling cascades which results in the expression of inflammatory mediators with the aim of eliminating the invading microbes. Most microbial pathogens contain multiple PAMPs which are recognized by different PRRs. the same PAMP may activate different PRRs. the host immune response has the ability to coordinate both cell-type specific as well pathogen–specific responses
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