Molecular Pathology of Campylobacter

Abstract

Campylobacter spp. are globally prevalent zoonotic pathogens causing bacterial diarrheal diseases. Found in warm-blooded animals and diverse environments, they transmit to humans through contaminated water, food, or contact with diseased animals. Human campylobacteriosis, caused primarily by Campylobacter coli (C. coli) and Campylobacter jejuni (C. jejuni), manifests as gastroenteritis and ranks among the leading causes of global diarrheal diseases. These infections can lead to severe complications, including autoimmune disorders like Guillain-Barre syndrome (GBS). In animals, infections can result in clinical effects like abortions, liver disease, and infertility. Campylobacter spp. lack typical human disease virulence factors, suggesting that clinical symptoms in campylobacteriosis are primarily triggered by the host immune response. This chapter explores the intricate interactions between C. jejuni and host tissues, focusing on the molecular pathology and inflammatory responses elicited, with an emphasis on the involvement of immune cells. The gastrointestinal epithelial cells play a crucial role in the initial stage of responding to C. jejuni infections through adhesion and extracellular sensing. Toll-like receptors (TLRs) are involved in detecting invasive infections, triggering proinflammatory responses. Upon invasion, C. jejuni uses Campylobacter invasion antigens (Cia) to penetrate intestinal cells, leading to increased IL-8 secretion and neutrophil chemotaxis. The genotoxin cytolethal distending toxin (CDT) and CRISPR-associated gene 9 (CjeCas9) contribute to host DNA disruption, apoptosis, and inflammation. Neutrophils, eosinophils, and mast cells play roles in tissue damage, with neutrophils restricting C. jejuni growth and eosinophils exhibiting activation responses. The adaptive immune response involves B and T lymphocytes generating antibodies and cytotoxic T cells respectively. Monocytes/macrophages, dendritic cells, and natural killer (NK) cells act as key players bridging innate and adaptive immunity, with various roles in inflammation, tissue repair, and modulating immune responses. NK cells interact with C. jejuni components to suppress inflammation and coordinate T lymphocyte responses. Understanding these complex interactions is crucial for unraveling the mechanisms underpinning Campylobacter-induced tissue pathology and inflammation, paving the way for advancements in disease management and prevention.