The Role of Toll-Like Receptors in the Production of Cytokines by Human Lung Macrophages

Abstract

Background: The Toll-like receptor (TLR) family is involved in the recognition of and response to microbial infections. These receptors are expressed in leukocytes. TLR stimulation induces the production of proinflammatory cytokines and chemokines. Given that human lung macrophages (LMs) constitute the first line of defense against inhaled pathogens, the objective of this study was to investigate the expression and function of TLR subtypes in this cell population. Methods: Human primary LMs were obtained from patients undergoing surgical resection. The RNA and protein expression levels of TLRs, chemokines, and cytokines were assessed after incubation with subtype-selective agonists. Results: In human LMs, the TLR expression level varied from one subtype to another. Stimulation with subtype-selective agonists induced an intense, concentration- and time-dependent increase in the production of chemokines and cytokines. TLR4 stimulation induced the strongest effect, whereas TLR9 stimulation induced a much weaker response. Conclusions: The stimulation of TLRs in human LMs induces intense cytokine and chemokine production, a characteristic of the proinflammatory M1 macrophage phenotype.

Innate Immune Responses to Highly Pathogenic Coronaviruses and Other Significant Respiratory Viral Infections

“…This barrier includes cells of the pulmonary epithelium and tissue-resident macrophages and dendritic cells (DCs). The macrophages and DCs express pattern recognition receptors (PRRs) that can detect molecules from pathogens (Pathogen-Associated Molecular Patterns-PAMPs) or molecules released from damaged cells (Damage or Danger-Associated Molecular Patterns-DAMPs) (158)(159)(160). In the lung, there are two populations of macrophages, alveolar and interstitial macrophages (161).…”

Metabolic reprograming of LPS-stimulated human lung macrophages involves tryptophan metabolism and the aspartate-arginosuccinate shunt

“…Human lung macrophages were isolated and cultured as previously described [1]. 2 million cells were cultured for 24 hrs in medium alone or with 10 ng.mL -1 LPS.…”

“…They are major effectors of the immune response as they express membrane receptors, including Toll-like receptors (TLRs), able to recognize conserved microbial ligands [1]. Once activated, TLRs induce the production of a pattern of cytokines, chemokines and mediators, such as metabolites from the arachidonic acid pathway, involved in the inflammatory response and characteristics of a macrophage engagement towards a M1 polarization state [1,2]. Lipopolysacharide (LPS) is the archetypal TLR ligand for the induction of M1 macrophage polarization [1].…”

“…Once activated, TLRs induce the production of a pattern of cytokines, chemokines and mediators, such as metabolites from the arachidonic acid pathway, involved in the inflammatory response and characteristics of a macrophage engagement towards a M1 polarization state [1,2]. Lipopolysacharide (LPS) is the archetypal TLR ligand for the induction of M1 macrophage polarization [1]. Like allergens (e.g.…”

Innate Immunity of the Lung

“…Microbial recognition is central in innate immunity to respiratory infection, and Toll-like receptors (TLR) are an essential part of the pulmonary toolbox of innate immunity that enables it to sense pathogen presence. Grassin-Delyle et al [5] studied expression and function of TLRs on human lung macrophages isolated from resected lung tissue. Expression of the diverse repertoire of TLRs and response to subtypespecific TLR agonists revealed a remarkably wide spectrum.…”