Abstract
Infection with EBV has been associated with various inflammatory disorders including inflammatory bowel diseases (IBD). Contribution of this virus to intestinal disease processes has not been assessed. We previously detected that EBV DNA triggers proinflammatory responses via the activation of endosomal Toll-like receptor (TLR) signaling. Hence, to examine the colitogenic potential of EBV DNA, we used the dextran sodium sulfate (DSS) mouse colitis model. C57BL/6J mice received either DSS-containing or regular drinking water. Mice were then administered EBV DNA by rectal gavage. Administration of EBV DNA to the DSS-fed mice aggravated colonic disease activity as well as increased the damage to the colon histologic architecture. Moreover, we observed enhanced expression of IL-17A, IFNγ and TNFα in colon tissues from the colitis mice (DSS-treated) given the EBV DNA compared to the other groups. This group also had a marked decrease in expression of the CTLA4 immunoregulatory marker. On the other hand, we observed enhanced expression of endosomal TLRs in colon tissues from the EBV DNA-treated colitis mice. These findings indicate that EBV DNA exacerbates proinflammatory responses in colitis. The ubiquity of EBV in the population indicates that possible similar responses may be of pertinence in a relevant proportion of IBD patients.
Highlights
Levels of Epstein–Barr virus (EBV) detected in Inflammatory Bowel Disease (IBD) inflamed tissues exceed what is expected based on the number of B lymphocytes-cells that harbor the virus-present in these tissues; while both the EBV viral load and the number of B lymphocytes are elevated in these inflamed tissues, these elevations are not proportionate to one another
dextran sodium sulfate (DSS) treatment resulted in decreased average mouse body with the highest average body weight loss of 6.4% observed in the group that was fed on DSS and that received the EBV DNA treatment (p = 0.0005) (Figure 2)
Growing evidence confirms that reactivation of EBV after latency can occur at any mucosal site where B cells reside
Summary
The Epstein–Barr virus (EBV) has been detected in multiple inflammatory gastrointestinal conditions including the two major types of IBD, Crohn’s disease and ulcerative colitis. Infection with EBV is associated with many types of cancers and various autoimmune diseases including rheumatoid arthritis (RA), multiple sclerosis and systemic lupus erythematosus [8]. This virus was reported to be present in the colon tissues of up to 44% of healthy controls but in 60–76% of colon tissues of IBD subjects with consequent odds ratios ranging from about 6 [9,10,11] to as high as 42 [12]. Several aspects of the involvement of EBV in these diseases remain to be elucidated including mechanisms it triggers in the host resulting in possible disease exacerbation
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