|Abner, S - MICHIGAN STATE UNIVERSITY|
|Turner, J - WAYNE STATE UNIVERSITY|
|Black, E - WAYNE STATE UNIVERSITY|
|Bartlett, P - MICHIGAN STATE UNIVERSITY|
|Mansfield, L - MICHIGAN STATE UNIVERSITY|
Submitted to: Journal of Parasitology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: June 1, 2001
Publication Date: August 1, 2002
Citation: Abner, S.R., Hill, D.E., Turner, J.R., Black, E.D., Bartlett, P., Urban Jr, J.F., Mansfield, L.S. Response of intestinal epithelial cells to trichuris suis excretory- secretory products and the influence on campylobacter jejuni invasion under in vitro conditions.. Journal of Parasitology. 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 (Altekruse et al., 1998). Diarrhea is the most common presenting symptom and is usually self-limiting within 5-7 days, although more severe consequences occur in immunocompromised hosts (Altekruse et al., 1998). Campylobacter infection is also the number one antecedent infection associated with development of Guillain-Barre syndrome, an autoimmune neuropathy (Buzby et al., 1997; Nachamkin et al., 1998). The primary source of human infection is improperly prepared poultry, but swine also harbor C. jejuni (Borch et al., 1996). The observation that opportunistic C. jejuni becomes invasive in conventionally-reared pigs infected with T. suis, swine whipworm (Mansfield and Urban, 1996), led us to pursue studies to determine the mechanisms of pathogenesis in this dual infection model. Our central hypothesis is that whipworm infection foster an environment conducive to Campylobacter invasion.
Technical Abstract: We have previously developed a swine animal model in which natural host resistance to Campylobacter jejuni is altered by experimental infection with low numbers of the nematode Trichuris suis. Pigs naturally colonized with C. jejuni experience colitis due to the invasion of the bacterium approximately 21 days following exposure to T. suis. 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.