Staphylococcus aureus protein A induced inflammatory response in human corneal epithelial cells

Abstract

In the present study, we examined the role of S. aureus protein A (SpA) in inducing inflammatory response in HCECs. Exposure of HCECs to SpA induces rapid NF-κB activation and secretion of proinflammatory cytokine/chemokines (TNF-α and IL-8) in both concentration and time-dependent manner. Challenge of HCECs with live SpA − / − mutant S. aureus strains resulted in significantly reduced production of the cytokines when compared to the wild-type S. aureus strain. SpA also elicited the activation of MAP Kinases P38, ERK, but not JNK, in HCECs. SpA-induced production of proinflammatory cytokine were completely blocked by the NF-κB and p38 inhibitors and partially inhibited by the Jnk inhibitor. Pretreatment with anti-TLR2 neutralizing antibody had no effect on SpA induced inflammatory response in HCECs, suggesting that this response is independent of TLR2 signaling. Moreover, unlike TLR2 ligands, SpA failed to induce the expression of antimicrobial peptides (hBD2 and LL-37) in HCECs. These studies indicate that SpA is a S. aureus virulence factor that stimulates HCEC inflammatory response through a pathway distinct from TLR2 in HCECs.

NF-κB Subtypes Regulate CCCTC Binding Factor Affecting Corneal Epithelial Cell Fate

“…Interestingly, CTCF activity is significantly suppressed by UV stress-induced NFB activation in apoptotic corneal epithelial cells (6). NF-B is activated in corneal epithelial cells through infection-and trauma-induced inflammation (4,30,(37)(38)(39). However, in our study, we also found that EGF-activated NF-B is directly involved in the regulation of CTCF.…”

“…Inflammation induces immune responses and stimulates production of pro-inflammatory cytokine/chemokines (tumor necrosis factor-␣ and interleukins 1, 6, and 8), which leads to activation of the mitogen-activated protein kinase cascades, such as ERK, c-Jun N-terminal kinase (JNK), and p38 signal pathways (6, 11, 30 -33). The downstream effect includes NF-B phosphorylation and subsequent translocation to the nucleus (30,32,34). There are five NF-B subtypes in mammalian cells, including RelA (p65), RelB, c-Rel, NF-B1 (p50), and NF-B2 (p52).…”

Response of corneal epithelial cells toStaphylococcus aureus

“…The observation that agonists of these receptors did not effect CCL20 expression by these cells would be consistent with the previous observation that little TLR2 occurs on the surface of the human cornea normally, 24 suggesting that S. aureus is sensed by these cells via another pathway. It was previously noted that protein A, which is expressed by S. aureus early in log phase, 43 is capable of stimulating TNFα and IL8 expression by corneal epithelial cells in a TLR2 independent fashion, 44 supporting this prospect.…”

Staphylococcus aureus lipoproteins trigger human corneal epithelial innate response through toll-like receptor-2

“…Upon contact with the ocular surface with compromised epithelial barrier, S. aureus activates the host cells such as the epithelia and initiates inflammatory response that is essential for containing infection in the cornea [8,19]. S. aureus cell wall-associated and secreted proteins (e.g., lipoproteins, protein A and hemolysins) [20][21][22] and cell wall components (e.g., peptidoglycan and lipoteichoic acid) [23,24] have been shown to cause inflammatory responses and, as such, may contribute to S. aureus keratitis. TLR2 has been shown to play a crucial role in the host response to S. aureus [15].…”