Helicobacter species induce different immune responses depending on the gut environment

Changes in the gut microbiota are involved in both homeostatic and inflammatory immune responses. T regulatory (T_reg) immune cells tolerate diverse bacterial communities, whereas inflammatory conditions activate T effector (T_eff) immune cells to react against the body’s own commensal microbiota. However, little is known regarding the role of commensal bacteria in inducing T_eff cells during inflammation.

A new study, led by Dr. Chyi-Song Hsieh from the Division of Rheumatology at the Department of Internal Medicine at Washington University School of Medicine in St. Louis (USA), has found that Helicobacter species that routinely interact with the host immune system may elicit either homeostatic or inflammatory immune responses depending on the gut environment.

The researchers studied T cell responses to commensal antigens during experimental colitis through analysing bacterial-reactive T cell receptor (TCR) transgenic cells and TCR repertoires in a murine colitis model.

The researchers found that Helicobacter species (pathobionts) are important inducers of T cell responses during both homeostasis and colitis. In pathogen-free mice that were not experiencing inflammation, T_reg cells were primed to recognize Helicobacter. Previous research has also shown that Helicobacter spp. are important inducers of antigen-specific T_reg cells during homeostasis. However, in the murine colitis model, Helicobacter exposure induced pro-inflammatory T_eff responses. Furthermore, Helicobacter also elicited an inflammatory response mediated via T_eff cells in lymphopenic mice. These results show that T_eff cell responses during experimental colitis or lymphopenia occur as a result of commensal antigens normally presented to the immune system during homeostasis and are context-dependent.

Secondly, the ability of gut commensal bacteria to induce T cell responses varied depending to their anatomic location relative to the mucosal surfaces. Expansion of Bacteroidetes species -which congregate in the stomach lumen unlike mucosal-residing Helicobacter bacteria- during colitis did not elicit T_eff responses in rodents.

According to the authors, “next steps will be to further differentiate between inflammatory responses that are directed towards ‘self’ microbes versus those targeted against ‘foreign’ antigens”.

In conclusion, mucosal-associated Helicobacter species may elicit context-dependent T cell responses during homeostasis and colitis. T cell-mediated intestinal inflammation may be driven by commensal antigens that are always in contact with the host immune system rather than antigens normally excluded by the mucosal barrier.

Reference:

Chai JN, Peng Y, Rengarajan S, et al. Helicobacter species are potent drivers of colonic T cell responses in homeostasis and inflammation. Sci Immunol. 2017; 2(13). doi: 10.1126/sciimmunol.aal5068.