Monocyte Chemoattractant Protein-1 Production by Intestinal Myofibroblasts in Response to Staphylococcal Enterotoxin A: Relevance to Staphylococcal Enterotoxigenic Disease

Abstract

Food poisoning due to staphylococcal enterotoxins A and B (SEA and SEB) affects hundreds of thousands of people annually. SEA and SEB induce massive intestinal cytokine production, which is believed to be the key factor in staphylococcal enterotoxin enteropathy. MHC class II molecules are the major receptors for staphylococcal enterotoxins. We recently demonstrated that normal human subepithelial intestinal myofibroblasts (IMFs) express MHC class II molecules. We hypothesized that IMFs are among the first cells to respond to staphylococcal enterotoxins and contribute to the cytokine production associated with staphylococcal enterotoxin pathogenesis. We demonstrated here that primary cultured IMFs bind staphylococcal enterotoxins in a MHC class II-dependent fashion in vitro. We also demonstrated that staphylococcal enterotoxins can cross a CaCo-2 epithelial monolayer in coculture with IMFs and bind to the MHC class II on IMFs. IMFs responded to SEA, but not SEB, exposure with 3- to 20-fold increases in the production of proinflammatory chemokines (MCP-1, IL-8), cytokines (IL-6), and growth factors (GM-CSF and G-CSF). The SEA induction of the proinflammatory mediators by IMFs resulted from the efficient cross-linking of MHC class II molecules because cross-linking of class II MHC by biotinylated anti-HLA-DR Abs induced similar cytokine patterns. The studies presented here show that MCP-1 is central to the production of other cytokines elicited by SEA in IMFs because its neutralization with specific Abs prevented the expression of IL-6 and IL-8 by IMFs. Thus, MCP-1 may play a leading role in initiation of inflammatory injury associated with staphylococcal enterotoxigenic disease.

Role of intestinal myofibroblasts in HIV-associated intestinal collagen deposition and immune reconstitution following combination antiretroviral therapy

“…We, and others demonstrated that intestinal CD90 + stromal cells (myofibroblasts and fibroblasts, IMFs) are non-professional antigen presenting cells that are located beneath the epithelial basement membrane [35–38] and play a major role in the innate GI immune responses via signaling through TLR1-9 [39, 40]. These cells are important contributors to the wound healing process [41, 42].…”

Staphylococcus aureus and Staphylococcal enterotoxins in foodborne diseases

“…Emetic activity of SEs has, also, been attributed to a direct effect on intestinal epithelium or the stimulation of the emetic center via the vagus nerve (Le Loir et al 2003). Data from recent works revealed that SEA and SEB induced massive intestinal cytokine production, which was the key factor in the initiation of the inflammatory response and the diarrheal disease (Pinchuk et al 2007). …”

Activation of Adventitial Fibroblasts in the Early Stage of the Aortic Transplant Vasculopathy in Rat

“…In our previous study, the earliest expression of MCP-1 was found in adven- titial fibroblasts before the formation of atherosclerotic lesions in intima (5). It is reported that MCP-1 can stimulate conversion of the fibroblast phenotype to the myofibroblast phenotype (37), whereas myofibroblasts can produce MCP-1 (38). In this study, MCP-1 protein was initially expressed in adventitial fibroblasts 3 days after allograft (Fig.…”