Monocytes alter epithelial responses to bacterial products

Model intestinal epithelia exhibit rapid and robust induction of pro‐inflammatory gene expression in response to basolateral contact with bacterial flagellin. Such gene expression likely plays an important role in host defense against invasive flagellated pathogens. In contrast, model gut epithelia do not exhibit robust induction of anti‐bacterial gene expression in response to the canonical bacterial product lipopolysacharride (LPS) even when LPS is applied to the basolateral surface. Thus, it is not yet clear if and how intestinal epithelial cells might participate in the generation of a mucosal inflammatory response elicited by non‐flagellated bacteria. However, in vivo, the basolateral surface of epithelial cells exists in relatively close proximity to immune cells that might respond to LPS and, subsequently, potentially secrete cytokines that could activate epithelial cells. Thus, the goal of this study was to test whether the presence of mononuclear cells conferred epithelial cells with the ability to respond to LPS. Epithelial gene expression was measured via cDNA microarray analysis. We observed that, indeed, while epithelial cells exhibited no significant changes in gene expression in response to LPS (0 of 15,000 genes were upregulated more than 3‐fold at 4 h), they responded robustly to LPS in the presence of 1 monocyte per 5 epithelial cells in a manner that did not permit monocyte‐epithelial contact (over 150 genes were upregulated more than 3‐fold in response to 4h treatment with LPS in the presence of monocytes). Interestingly, the presence of monocytes also modulated epithelial gene expression in response to flagellin enhancing the expression of some genes and suppressing the expression of others. Thus, monocytes can alter epithelial responses to bacterial products, likely via secreted factors.