Campylobacter spp. are the leading cause of bacterial-derived gastroenteritis worldwide, impacting ninety-six million individuals annually. Unlike other bacterial pathogens of the gastrointestinal tract, Campylobacter spp. lack many of the classical virulence factors that are often associated with the ability to induce disease in humans, including an array of canonical secretion systems and toxins. As such, the clinical manifestations of human campylobacteriosis and its resulting gastrointestinal pathology are believed to be primarily due to the host immune response toward the bacterium. Further, while gastrointestinal infection is usually self-limiting, numerous post-infectious disorders can occur, including the development of Guillan-Barré syndrome, reactive arthritis, and irritable bowel syndrome. Because gastrointestinal disease likely results from the host immune response, the development of these post-infectious disorders may be due to dysregulation or misdirection of the same inflammatory response. As a result, it is becoming increasingly important to the Campylobacter field, and human health, that the cellular immune responses toward Campylobacter be better understood, including which immunological events are critical to the development of disease and the post-infectious disorders mentioned above. In this review, we will collectively cover the cellular immune responses across susceptible hosts to C. jejuni infection, along with the tissue pathology and post-infectious disorders which may develop.

Campylobacter jejuni infection of neutrophils results in differentiation of a subtype that activates HIF-1 and NF-κB in colonocytes and decreases TCRζ in T cells.

The discovery of neutrophil subtypes has expanded what is known about neutrophil functions, yet there is still much to learn about the role of these subtypes during bacterial infection. We investigated whether Campylobacter jejuni induced differentiation of human neutrophils into the hypersegmented, CD16hi/CD62Llo subtype. In addition, we investigated whether C. jejuni-dependent differentiation of this neutrophil subtype induced cancer promoting activities of human T cells and colonocytes, which were observed in other studies of hypersegmented, CD16hi/CD62Llo neutrophils. We found that C. jejuni causes a significant shift in human neutrophil populations to the hypersegmented, CD16hi/CD62Llo subtype and that those populations exhibit delayed apoptosis, elevated arginase-1 expression, and increased reactive oxygen species production. Furthermore, incubation of C. jejuni-infected neutrophils with human T cells resulted in decreased expression of the ζ-chain of the T cell receptor (TCRζ), which was restored upon supplementation with exogenous L-arginine. In addition, incubation of C. jejuni-infected neutrophils with human colonocytes resulted in increased HIF-1α stabilization and NF-κB activation in those colonocytes, which may result in the upregulation of pro-tumorigenic genes. This response, coupled with the ability of C. jejuni-infected neutrophils to suppress TCRζ expression in T cells, could result in the promotion of colorectal tumorigenesis during infection with C. jejuni.