## 3 Host-Pathogen Interactions in _Campylobacter_ Infections: Understanding the Link to PI-IBS
Despite IL-4 typically being regarded as anti-inflammatory, it has been hypothesized that, in the context of PI-IBS, IL-4 may facilitate antigen endocytosis, leading to prolonged immune activation [17]. A recent examination differentiated between two main types of \(\gamma\delta\) T cells: V81 \(\gamma\delta\) T cells, primarily located in local mucosal tissue, and V82 \(\gamma\delta\) T cells, which are predominant in peripheral blood [42]. Interestingly, in patients with PI-IBS, V81 \(\gamma\delta\) T cells, rather than V82 \(\gamma\delta\) T cells, were found to be dominant in both peripheral blood and colonic tissues. Additionally, these V81 \(\gamma\delta\) T cells displayed an enhanced capacity for proliferation, activation and production of IL-17 following IL-23 stimulation in PI-IBS patients [42]. These findings indicate that V81 \(\gamma\delta\) T cells are the primary \(\gamma\delta\) T cell subtype in both peripheral and intestinal tissues of PI-IBS patients and are significant producers of IL-17, suggesting their potential as novel therapeutic targets for managing PI-IBS. Further investigations have identified increased concentrations of IFN-\(\gamma\), IL-10 and TNF-\(\alpha\) alongside decreased levels of IL-10 and IL-13 in the mucosa of individuals with PI-IBS, highlighting an imbalance between anti-inflammatory and pro-inflammatory mediators [17]. This disequilibrium may exacerbate TJ dysfunction and epithelial permeability, perpetuating a harmful cycle. Others have identified a greater prevalence of CD8+ T cells and resident macrophages in the intestinal mucosa of PI-IBS patients with a history of _Sligella_ infection than in those with non-IBS infection [43]. This persistent elevation in CD8+ T cells and macrophages, primed for activation by specific antigens, is believed to contribute to the ongoing gut inflammation and distress state. In a PI-IBS murine model induced by _Trichiella spiralis_, investigators noted that dendritic cells within the lamina propria displayed heightened expression of co-stimulatory molecules and an augmented capacity to stimulate and attach to CD4+ T cells, a phenomenon closely linked with sustained visceral hypersensitivity [44]. Individuals diagnosed with PI-IBS exhibit distinct gastrointestinal changes when compared to those with sporadic IBS [41]. One earlier comparative analysis showed two distinct differences between cases of PI-IBS following _Campylobacter_ infection and those attributed to other pathogens like _Salmonella_ and _Sligella_[45]. The most significant change was a 3.71-fold increase in IgG antibodies targeting vinculin, a human cell adhesion protein, among individuals previously infected with _Campylobacter_ spp. This correlation between anti- vinculin antibodies and post-_Campylobacter_ IBS is particularly compelling. Previousresearch has linked the internalization of _C. jejuni_ with vinculin, and emerging data suggest that anti-viculin antibodies could act as a biomarker for IBS [45]. Consistency in the relationship between _Campylobacter_ infections and the presence of anti-viculin antibodies has been observed across different studies, including an evaluation of military personnel conducted in 2015 [28]. This study detected elevated levels of anti-viculin antibodies in individuals who developed PI-IBS following a _Campylobacter_ infection. Similarly, an earlier study reported increased anti-_CdtB_ and anti-viculin antibodies in patients with PI-IBS [28]. Likewise, PI-IBS cases of post-_Shigella_ gastroenteritis exhibited a heightened count of mast cells in the terminal ileum. These cells emit mediators like histamine, IL-1\(\beta\), IL-6 and TNF-\(\alpha\), which have the potential to activate or sensitize visceral nociceptors, thereby contributing to the abdominal discomfort and pain characteristic of PI-IBS [7]. Notably, an excessive release of IL-8, triggered by the body's recognition of pathogen-associated LOS, marks the pathogenesis of _Campylobacter_ infections [46].