Direct Manipulation of T Lymphocytes by Proteins of Gastrointestinal Bacterial Pathogens

Abstract

Gastrointestinal bacterial infection represents a significant threat to human health, as well as a burden on food animal production and welfare. Although there is advanced knowledge about the molecular mechanisms underlying pathogenesis, including the development of immune responses to these pathogens, gaps in knowledge persist. It is well established that gastrointestinal bacterial pathogens produce a myriad of proteins that affect the development and effectiveness of innate immune responses. However, relatively few proteins that directly affect lymphocytes responsible for humoral or cell-mediated immunity and memory have been identified. Here, we review factors produced by gastrointestinal bacterial pathogens that have direct T cell interactions and what is known about their functions and mechanisms of action. T cell-interacting bacterial proteins that have been identified to date mainly target three major T cell responses: activation and expansion, chemotaxis, or apoptosis. Further, the requirement for more focused studies to identify and understand additional mechanisms used by bacteria to directly affect the T cell immune response and how these may contribute to pathogenesis is highlighted. Increased knowledge in this area will help to drive development of better interventions in prevention and treatment of gastrointestinal bacterial infection.

Keywords: T cell; bacteriology; enteric infection.

FIG 1

GALT and T cell distribution in the intestine. Immune responses in the intestine are controlled mainly by gut-associated lymphoid tissue (GALT), including the Peyer's patches, mesenteric lymph nodes, and isolated lymphoid follicles in the mucosa and lamina propria. The mucosa is also studded with intraepithelial lymphocytes. Naive T cells can be recruited from the circulation to lymphoid organs in the intestines, where they can be activated.

FIG 2

Summary of T cell-interacting bacterial proteins and their targets. The majority of bacterial proteins that interact with T cells are directed at modifying activation/proliferation; however, there are some proteins that affect chemotaxis and apoptosis. Where the key affected molecules are known, these are indicated; however, the details of a number of molecules remain unknown. Bacterial protein names are bounded by gray boxes. sAg, superantigen (Staphylococcus); CT, cholera toxin (Vibrio cholerae); GGT, gamma glutamyl transferase (H. pylori and C. jejuni); IpgD, invasion plasmid gene D (Shigella); LifA, lymphocyte-inhibiting factor A (E. coli); LT, heat-labile toxin (E. coli); STM3106, asparaginase (Salmonella); APC, antigen-presenting cell; MHC, major histocompatibility complex; YopH, Yersinia outer protein H (Yersinia); VacA, vacuolating cytotoxin A (H. pylori); TCR, T cell receptor.