Guardians of the Gut: Newly Appreciated Role of Epithelial Toll-Like Receptors in Protecting the Intestine

Chronic epithelial TLR activation promotes expression of fecal IgA. Constitutive activation of epithelial TLR signaling results in NF-κB–mediated production of B-cell chemoattractants, CCL20 and CCL28, that recruit B lymphocytes. TLR signaling may also result in production of APRIL, which promotes B-cell differentiation into IgA-producing plasma cells (PC).

TLR signaling can promote both survival and tumor necrosis. Activation of TLR-5 in carcinomas may simultaneously (1) promote cancer cell survival via activating NF-κB–mediated anti-apoptotic gene expression and (2) recruit neutrophils that promote tumor necrosis. Whether necrosis or survival prevails will likely depend on the specific characteristics of a particular tumor.