Toll‐like receptor 2 (TLR2) and TLR4 differentially activate human mast cells

Abstract

In the present report we have analyzed whether human normal cord blood-derived mast cells (CBMC) could interact with bacterial products, especially lipopolysaccharide (LPS) from Escherichia coli and peptidoglycan (PGN) from Staphylococcus aureus, known as Tolllike receptor (TLR) 4 and TLR2 agonists, respectively. We found that both LPS and PGN induced significant release of not only tumor necrosis factor- § (TNF- § ), but also IL-5, IL-10 and IL-13 by human mast cells (MC). We also established that the stimulation of CBMC with LPS or with PGN is mediated through interactions with TLR4 or with TLR2, respectively. Thus, our data indicate that activation of either TLR2 or TLR4 pathway may lead to a pro-Th2 immune response. However, the release of TNF- § induced by LPS, conversely to PGN, required the priming of CBMC by IL-4 and the presence of serum components, in particular soluble CD14. Of interest, stimulation by PGN, but not by LPS, induced release of histamine by human MC. Altogether, these findings provide the first evidence that human MC differentially respond towards bacterial components, and that their responses depend on TLR pathways and reveal human specificities in the pattern of cytokine production.

Human mast cells promote colon cancer growth via bidirectional crosstalk: studies in 2D and 3D coculture models

“…43,44 Furthermore, many TLR2 expressing cells are present in CRC stromal. 45 In line with the data of Varadaradjalou et al, 46 we show that primary human MC constitutively express TLR2 (Supplemental Figure 1B). To mimic the inflammatory microenvironment in tumor, we pre-stimulated human MC with TLR2 agonist FSL-1 and co-cultured these MC with HT29 spheroids.…”

“…It has been reported that TLR2 agonists induce the release of TNF-a, IL-5, IL-10 and IL-13 by human MC. 46 Nevertheless, we did not detect measurable amount TNF-a, IL-5, IL-10 and IL-13 in the 3D coculture, which might be due to the different source of cultured human MC. Interestingly, TLR2-primed MC significantly enhanced angiogenin and IL-8 production in the co-culture with HT29.…”

Activation of mast cells by double-stranded RNA: evidence for activation through Toll-like receptor 3

“…32 We have also confirmed previous findings showing that human MCs express TLR-1, TLR-2, TLR-4, and TLR-6, all of which are involved in LPS-mediated and peptidoglycanmediated signaling. 2,3 Therefore, mature human MCs express all but 2 TLRs, suggesting that they are able to participate in innate immune response to a wide variety of pathogens. Because MCs are resident in all peripheral tissues and because they are long-lived, it is likely that their response to viral infection may contribute significantly to localized innate immune response to viral infection.…”

“…1 Indeed, MCs of human and rodent origin have been shown to express Toll-like receptor (TLR)e1, TLR-2, TLR-4, and TLR-6 mRNA and to respond to lipopolysaccharide and peptidoglycan by producing TNF-a, GM-CSF, IL-1b, IL-5, IL-13, and leukotriene C 4 . 2,3 Although these studies suggest that MCs contribute to innate immune responses against invading bacteria, little is known regarding the interaction of MCs with viruses or their products, and whether this interaction results in the production of innate cytokines like type I IFNs, known to play critical roles in host defense against viral infection via both virocidal and immunoregulatory properties.…”

R‐form LPS, the master key to the activation ofTLR4/MD‐2‐positive cells

“…The expression of CD14 on MC is still a matter of dispute [29][30][31][32][33][34]. To see if the difference observed between the capacity of S-and R-form LPS to activate MC might be related to a differential requirement for CD14 and LBP by the two LPS, we investigated the expression of mCD14 on MC by FACS analysis using cells from CD14 -/-mice as negative control (Fig.…”