Early Intestinal Epithelial Response to Toxoplasma gondii Infection (39.29)

Abstract

Abstract Intestinal epithelial cells are critical for nutrient uptake, but also provide a physical and chemical barrier to infection. When that barrier is breached, epithelial cells can respond and regulate local and systemic immune responses. Toxoplasma gondii (T. gondii) is an orally acquired apicomplexan protozoan intracellular parasite that first encounters intestinal epithelium and then disseminates systemically. Little is known about the responses elicited early during infection in the intestine since studies to date have focused primarily on systemic immune responses through intraperitoneal infection. Furthermore, we lack information on the response of human intestinal cells to live T. gondii infection. Here we examined the early response of human intestinal epithelial cells following infection with T. gondii. Using an in vitro system, we show that human small intestinal epithelial cells infected with T. gondii elicit rapid MAPK phosphorylation, NF-κB nuclear translocation, and secretion of interleukin (IL)-8. Both ERK1/2 activation and IL-8 secretion responses were PI3 kinase-independent yet MyD88- and TLR2-dependent. Although parasite genotype correlates with pathogenicity in mice, all genotypes of T. gondii elicited a similar response through TLR2 and MyD88. Oocysts of T. gondii stimulated cells via TLR2, similar to tachyzoites. Furthermore, we were able to identify many T. gondii-regulated genes in the infected cells using a pathway-focused array. Together, our findings suggest that intestinal epithelial cells recognize and respond to T. gondii during infection, the outcome of which likely modulates intestinal and systemic immunity.