## 3 Host-Pathogen Interactions in _Campylobacter_ Infections: Understanding the Link to PI-IBS
However, contrasting findings from a larger study on the Walkerton water outbreak indicated that only 16% of PI-IBS patients exhibited increased permeability [32]. This sustained increase in intestinal permeability is a precursor to low-grade immune activation. Although a baseline level of physiological inflammation is normal, research in individuals with IBS and PI-IBS has identified ongoing low-grade intestinal immune activation. Alterations in the innate immune system, particularly in mast cells and macrophages within the intestinal mucosa of PI-IBS patients, have been noted. Specifically, the increase in immune cells, including mast cells, macrophages, monocytes, T lymphocytes and intraepithelial lymphocytes, has been recorded for up to five years, tracking infection [10]. Starting from day 11 of human post-infection, B lymphocytes significantly increase the production of circulating antibodies, predominantly targeting the flagellin of _C. jejuni_ as their epitope [40]. These antibodies remain detectable in circulation for up to one year following the initial infection [40]. Furthermore, colonic supernatants from PI-IBS patients hold the capacity to activate mast cells, which are recognized as key mediators of visceral hypersensitivity in IBS [10]. For instance, PI-IBS patients show a decrease in resident CD68 and calprotectin-positive macrophages compared to healthy controls [27]. Furthermore, an increase in mast cells closely associated with nerve fibers in the terminal ileum mucosa has been observed in PI-IBS patients, with studies suggesting a link between this close nerve-mast cell interaction and symptoms such as abdominal bloating and pain [27]. Substantial evidence indicates intestinal mucosa damage constitutes a major reaction to PI-IBS. Such damage is as a precursor to establishing a low-grade inflammatory state [27; 41]. The increase in permeability indicates a compromise in the normal gut barrier function, facilitating the entry of bacterial products into the lamina propria [30]. A heightened gut permeability function could further contribute to immune dysregulation and nerve hypersensitivity. The damage to nerves and subsequent nerve remodeling has the potential to influence both motility and secretion, underscoring the complex interplay of factors contributing to the pathophysiology of PI-IBS [30]. Vulnerability to infection has been associated with the composition of the microbiota. This sequence of events allows antigens to penetrate the mucosa from the lumen, initiating immune stress and producing inflammatory cytokines, furthering the cycle of inflammation and symptomatology associated with PI-IBS. A current multivariate analysis revealed an association between PI-IBS and elevated C-reactive protein (CRP) levels [18]. This finding has led to speculation that high CRP levels might play a role in developing PI-IBS by indicating more severe inflammation and potentially signaling the presence of mucosal damage. Moreover, alterations in the levels of various cytokines, such as IL-2, IL-6 and iIL-10, along with transforming growth factor beta (TGF-\(\beta\)), and changes in the expression of toll-like receptors (TLRs) 2, 4, 7, 8 and 9, have been reported as specific markers of a post-infectious condition [21]. The activation of cellular NF-\(\kappa\)B signaling pathways, similar to the response elicited by other relatively benign bacteria, can be initiated by interacting pathogen-associated molecular patterns (PAMPs) with cellular TLR [36]. This mechanism may reflect a broader, more generalized tissue immune response to infection, indicating a commonality in the host's defense strategy against a diverse array of microbial pathogens. Immunohistochemical analyses of mucosal samples from PI-IBS patients have revealed the antigen-induced secretion of interleukins IL-4, IL-8, IL-1\(\beta\) and IL-22 by epithelial cells [1,30].