β-Glucan–Activated Human B Lymphocytes Participate in Innate Immune Responses by Releasing Proinflammatory Cytokines and Stimulating Neutrophil Chemotaxis

Abstract

B-lymphocytes play an essential regulatory role in the adaptive immune response through antibody production during infection. A less known function of B-lymphocytes is their ability to respond directly to infectious antigens through stimulation of pattern recognition receptors expressed on their surfaces. β-glucans are carbohydrates present in the cell wall of many pathogenic fungi that can be detected in the peripheral blood of patients during infection. They have been shown to participate in the innate inflammatory response as they can directly activate peripheral macrophages and dendritic cells. However, their effect as direct stimulators of B-lymphocytes has not been yet fully elucidated. The aim of this study was to examine the molecular mechanisms and cytokine profiles generated following β-glucan stimulation of B-lymphocytes, compared with the well-established TLR-9 agonist CpG-oligodeoxynucleotide (CpG) and study the participation of β-glucan stimulated B-cells in the innate immune response. Herein, we demonstrate that β-glucan activated B-lymphocytes upregulate pro-inflammatory cytokines (TNFα, IL-6 and IL-8). Interestingly, β-glucan, unlike CpG, had no effect on B-lymphocyte proliferation or IgM production. When compared with CpG (TLR9 agonist), β-glucan-activated cells secreted significantly higher levels of IL-8. Furthermore, IL-8 secretion was partially mediated by Dectin-1 and required SYK, MAPKs and the transcription factors NF-κB and AP-1. Moreover, we observed that conditioned media from β-glucan stimulated B-lymphocytes elicited neutrophil chemotaxis. These studies suggest that β-glucan activated B-lymphocytes have an important and novel role in fungal innate immune responses.

Euglena gracilis paramylon activates human lymphocytes by upregulating pro‐inflammatory factors

“…; Ali et al. ). Then, we assessed NO production by stimulated PBMC, since iNOS‐derived NO is an important cellular signaling molecule secreted as free radical (Lechner et al.…”

Regulation of Gene Expression by β-Glucans

“…Human monocyte-derived β-glucan from baker's yeast (Cardone et al, 2014) Agilent-014850 Whole Human RPS18, EGR1, NFKBID, DCs from healthy donors (Sigma-Aldrich) 10 µg mL IL12B,IL12A,EB13,ITGB8,IL27,IL15,CD38,CD80,CCR7,STAT3,IRF1,TNF,CCL4,IL10,IL20,IL23,NFKB1A,NFKBIZ,PTGS2,TLR2,SOD2,NFKB1,IL6,IL1B,IL6,IL8,IL12, Human B lymphocytes Curdlan (Sigma-Aldrich) (Ali et al, 2015) IL-8 expression was shown to IL18 isolated from healthy 100 ug mL −1 for 24 h involve Dectin-1, SYK, MAPKs donors and transcription factors AP-1 and NF-kB GITRL protein Murine DCs whole β glucan particles from (Tian et al, 2012) TNFSF18is the gene for GITRL, S. cerevisiae treated for 48 h a cytokine in the TNF ligand (100 µg mL…”

“…While most studies have focused on the activation of gene expression in DCs, a recent report demonstrated that purified β-glucan (curdlan) induces expression of several cytokines including TNFα, IL-6 andIL-8 in human B lymphocytes at both the mRNA and protein level (Ali et al, 2015). Activation of IL-8 was shown to be mediated through the Dectin-1 receptor and involved SYK, ERK and JNK and activation of the transcription factors AP-1 and NFκB.…”

“…Activation of IL-8 was shown to be mediated through the Dectin-1 receptor and involved SYK, ERK and JNK and activation of the transcription factors AP-1 and NFκB. Interestingly, β-glucan had no effect on antibody production or proliferation suggesting that β-glucans induce a different response than TLR-9 agonist CpG oligodeoxynucleotide (CpG) that is a bacterial and viral DNA component known to induce cytokine production in B lymphocytes (Ali et al, 2015).…”

Effect of Coriolus versicolor glucan on the stimulation of cytokine production in sarcoma-180-bearing mice

“…Among the diverse glucans present in mushrooms are α-glucans, which have also been identified in parasitic and bacterial cell communities (14). Notably, glucans have been indicated to increase the secretion of a range of key cytokines, including interleukins (ILs) and interferons (IFNs) (15,16). Our group previously demonstrated the anticancer and immunomodulatory activities of a glucan from CV with potential as a therapeutic in cancer treatment (3).…”