Submitted to: International Journal for Parasitology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 6/1/2001
Publication Date: N/A
Citation: Interpretive Summary: Campylobacter jejuni is the most commonly isolated human enterobacterial pathogen in the United States, causing an estimated four million cases of enteritis per year. The primary source of human infection is improperly prepared poultry, but swine also harbor C. jejuni. The observation that opportunistic C. jejuni becomes invasive in conventionally-reared pigs infected with T. suis, the swine whipworm (Mansfield and Urban, 1996), led to studies to determine the mechanisms of pathogenesis in this dual infection model. The present study tested the hypothesis that T. suis ESP affects IECs causing enhanced C. jejuni invasion similar to that observed in the dual infection pig model. Cell lines of pig and human origin were used to investigate the effect of T. suis ESP on IECs under in vitro conditions. In addition, invasion of C. jejuni in IECs was measured in the presence and absence of ESP to determine if ESP rendered IECs more permissive for C. jejuni internalization. These data support a mechanism by which T. suis disrupts the integrity of the IEC barrier, which leads to lowered natural resistance to opportunistic pathogens such as C. jejuni.
Technical Abstract: To better understand the mechanism of T. suis-dependent C. jejuni colitis, we evaluated the effects of T. suis excretory-secretory products (ESP) on intestinal epithelial cells (IECs) and the influence of ESP on C. jejuni invasion in IECs under in vitro conditions. Viability assays, based on the MTT method, revealed a dose-dependent cytotoxic response in ESP-treated IECs. IPEC-1 and INT407 were more sensitive to T. suis ESP than Caco-2 cells. Independent of cell death, transepithelial electrical resistance (TER) dropped significantly in IPEC-1 cells treated on apical and basolateral surfaces, but not those treated only on apical surfaces. Using the gentamicin killing assay, reduced numbers of intracellular C. jejuni were recovered from IECs treated with ESP. This observation can be explained by a direct antibacterial activity in ESP, active at concentrations as low as 10 mg protein/ml, which may function to assist worms in defense against pathogens. In addition to mechanical damage from worms, these results suggest that soluble products released by T. suis contribute to IEC damage at the site of worm attachment.