Differences in innate immune responses upon stimulation with gram‐positive and gram‐negative bacteria

Abstract

Background and Objectives: Host recognition pathways for gram‐negative and gram‐positive bacteria comprise pattern recognition receptors among which Toll‐like receptors (TLRs) play a pivotal role. TLRs share common signaling pathways yet exhibit specificity as well. Periodontal disease is initiated and maintained in the first line by gram‐negative but also gram‐positive bacterial infection of the gingival sulcus. To date only limited information is available on whether gram‐positive and gram‐negative bacteria induce different host responses (strength or quality). Materials and methods: To elucidate these differential effects we focused on proinflammatory cytokine releases by assessing ex vivo stimulation of whole blood with heat‐killed gram‐negative and gram‐positive bacteria and thereof derived microbial products associated with distinct TLRs. Tumor necrosis factor‐α and interleukin‐8 release were measured in the supernatants by enzyme‐linked immunosorbent assay. In addition, innate immune responses of peritoneal macrophages from mice lacking TLR2 and TLR4 were tested. Results: We observed that gram‐negative and gram‐positive species induced distinct patterns of cytokine production. Gram‐negative species produced higher amounts of tumor necrosis factor‐α while gram‐positive species released higher amounts of the chemokine interleukin‐8. Data from TLR knockout mice and TLR‐transfected HEK cells revealed a somehow specific role of TLR4 and TLR2 for the recognition of gram‐negative and gram‐positive bacteria, respectively, an observation that goes along with the dominant recognition of the respective pathogen associated molecular patterns lipopolysaccharide and lipoteichoic acid. Conclusions: The results show that gram‐negative and gram‐positive bacterial species induce different patterns of immunoregulatory activity, which might be the result of activation of different TLRs.

Diverse Toll-Like Receptors Mediate Cytokine Production by Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans in Macrophages

“…There are inconsistent results among studies regarding the involvement of TLR2 and TLR4 in F. nucleatum-and A. actinomycetemcomitans-induced immune responses. Previous reports have shown that F. nucleatum-induced production of TNF-␣ and reactive oxygen species (ROS) was significantly lower in thioglycolate-elicited peritoneal macrophages from TLR2-deficient or TLR4-mutant (C3H/H3J) mice than from control WT cells (13,14). In human periodontal ligament (HPDL) cells, F. nucleatum-mediated production of cytokines and chemokines was reduced by treatment with TLR2 and TLR4 neutralizing antibodies (6).…”

“…In addition, two studies revealed that both TLR2 and TLR4 mediate A. actinomycetemcomitans-induced production of cytokines and chemokines in HPDL or transfected HEK cells (5,6). On the other hand, in a study by Tietze et al, A. actinomycetemcomitans induced only TLR2 activity, and not TLR4, resulting in NF-B activation in transfected HEK cells (14). These discrepancies seem to be due to different experimental conditions, such as the type of cells used, bacterial strains, and assay methods.…”

Expression Profiles of Genes in Toll-Like Receptor-Mediated Signaling of Broilers Infected with Clostridium perfringens

“…These results are consistent with observations for mammals, in which gram-positive bacteria present a tendency for signaling through the TLR2 pathway. Signaling via TLR4 was also observed, however, to a lesser extent (38). C. perfringens infection occurs in the small intestines of chickens.…”

Myricetin blocks lipoteichoic acid-induced COX-2 expression in human gingival fibroblasts

“…HGFs are thought to play an important role in promoting inflammatory responses. Toll-like receptors (TLRs) play a significant role in PAMP recognition and the induction of molecules that act primarily to reduce the action of pathogens, but also favor the production of pro-inflammatory molecules and the development of chronic periodontitis [12][13][14][15]. Lipoteichoic acid (LTA) is a pathogen-associated molecular pattern obtained from Gram-positive bacteria.…”