Uncoupling of Pro- and Anti-Inflammatory Properties of Staphylococcus aureus

Abstract

Staphylococcus aureus is a Gram-positive bacterium that is carried by a quarter of the healthy human population and that can cause severe infections. This pathobiosis has been linked to a balance between Toll-like receptor 2 (TLR2)-dependent pro-and anti-inflammatory responses. The relationship between these two types of responses is unknown. Analysis of 16 nasal isolates of S. aureus showed heterogeneity in their capacity to induce pro-and anti-inflammatory responses, suggesting that these two responses are independent of each other. Uncoupling of these responses was corroborated by selective signaling through phosphoinositol 3-kinase (PI3K)-AktmTOR and extracellular signal-regulated kinase (ERK) for the anti-inflammatory response and through p38 for the proinflammatory response. Uncoupling was also observed at the level of phagocytosis and phagosomal processing of S. aureus, which were required solely for the proinflammatory response. Importantly, the anti-inflammatory properties of an S. aureus isolate correlated with its ability to modulate T cell immunity. Our results suggest the presence of anti-inflammatory TLR2 ligands in the staphylococcal cell wall, whose identification may provide templates for novel immunomodulatory drugs.

IL-10 Plays Opposing Roles during Staphylococcus aureus Systemic and Localized Infections

“…S. aureus-induced IL-10 production by monocytes/macrophages is critically TLR2 dependent and, importantly, it appears that S. aureus-induced pro-and antiinflammatory cytokine production by these cells can be uncoupled due to the organism's capacity to manipulate TLR2 plasticity and engage unique downstream signaling pathways (33). We now demonstrate that IL-10 production by B1a cells is also TLR2 dependent.…”

“…8A). Previous studies have indicated that S. aureus-induced IL-10 production by macrophages is TLR2 dependent (33). To investigate a potential role for TLR2 in B1a cell activation by S. aureus, we cultured naive B1a cells isolated from WT or TLR2 2/2 mice in the presence of live S. aureus (MOI of 100).…”

Interactions of Klebsiella pneumoniae with the Innate Immune System Vary in Relation to Clone and Resistance Phenotype

“…More precisely (16), MDR E. coli induced a potent early production of proinflammatory cytokines, followed by low release of IL-10; this was accompanied by prolonged survival in an experimental sepsis model in rabbits much resembling the findings of K. pneumoniae. Peres et al (17) showed that Staphylococcus aureus isolates have differential capacities to induce pro-and anti-inflammatory cytokine production by human monocytes, implicating that these responses may determine colonization and disease tolerance versus pathogenicity and disease.…”

Toll-like receptor 2: An important immunomodulatory molecule during Helicobacter pylori infection

“…Staphylococcus aureus (S. aureus) induces the production of IL-10 by monocytes, macrophages and B1a cells in a TLR2-dependent manner [125,126]. IL-10 contributes in pathologic events during acute localized S. aureus infection by inhibiting local proinflammatory cytokine production.…”