Elevated iron status increases bacterial invasion and survival and alters cytokine/chemokine mRNA expression in Caco-2 human intestinal cells

iron status affects both microbial growth and immune function. Mammalian ir on homeostasis is maintained primarily by regulating the absorption of the micronutrient in the proximal small intestine. The iron concentration of th e enterocyte can fluctuate widely in response to both dietary and whole bod y iron status, as well as in response to infections. The possibility that a n enterocyte with an elevated iron concentration is more susceptible to inv asion by enteric pathogens is not known. Therefore, we examined the impact of enterocyte iron status on the invasion and survival of an enteric pathog en, as well as on the levels of several cytokine and chemokine mRNAs by the host cell. The enterocyte-like Caco-2 human intestinal cell line and Salmo nella enteritidis served as the models to examine the effect of iron on the host-parasite interaction. Iron status of Caco-2 cells was altered by incu bation in serum-free medium supplemented with varying levels of iron. Eleva ted iron status of Caco-2 cells increased the efficiency of the invasion an d the number of bacteria surviving in the intracellular environment. Caco-2 cells constitutively expressed transforming growth factor-beta1, interleuk in-8, monocyte chemotactic protein-1, tumor necrosis factor-alpha and inter leukin-1 beta, and infection with S. enteritidis increased the relative qua ntities of all cytokine/chemokine mRNAs except interleukin-1 beta. Elevated iron status of Caco-2 cells decreased the levels of cytokine/chemokine mRN As by 25-45% in uninfected cells. In contrast, bacterial infection was asso ciated with a 21-95% increase in cytokine/chemokine mRNAs levels in Caco-2 cells with higher iron concentration compared with infected cells with lowe r iron concentration. These data support the hypothesis that elevated enter ocyte iron status increases susceptibility to infection and exacerbates the mucosal inflammatory response initiated by microbial invasion by increasin g cytokine/chemokine expression.