Study Unravels Cause of Compromised Immunity in Gastric Patients

Helicobacter pylori bacteria is associated with chronic inflammation in the stomach area, and is involved in ulcers, mucosa-associated lymphoid tissue lymphoma (MALT), which can develop into gastric malignancies. A new study, conducted by the researchers at the Indian Institute of Technolgy (IIT), Indore, reveals how Helicobacter pylori (H. pylori) infected gastric patients suffered from compromised immunity.

Researchers demonstrated the involvement of HomA and HomB, outer membrane proteins (OMPs) of Helicobacter pylori, in the modulation of immune cell functioning, where they have illustrated the molecular mechanism of B-cells immune suppression.

The research findings are based on two separate studies, which have been published in research journals Nature Scientific Reports and Molecular Immunology. These studies, led by Dr Prashant Kodgire, in collaboration with Dr Amit Kumar (IIT Indore), and Dr Ravindra Makde, Scientist at Raja Ramanna Centre for Advanced Technology (RRCAT), Indore, was conducted by the Molecular Immunology Group, IIT, Indore.

The human immune system can be broadly classified as innate, humoral and cellular immune players, where different cells independently play a vital role. Additionally, these cells together demonstrate a synergetic role via communicating with each other. B-cell and T-cell communication are very crucial for immune system activation and proper function, which finally leads to neutralization and killing of pathogens.

Helicobacter pylori bacteria is associated with chronic inflammation in the stomach area, and is involved in ulcers, mucosa-associated lymphoid tissue lymphoma (MALT), which can develop into gastric malignancies. A new study, conducted by the researchers at the Indian Institute of Technolgy (IIT), Indore, reveals how Helicobacter pylori (H. pylori) infected gastric patients suffered from compromised immunity.

Generation of antibody diversity and their production are specifically confined to B-cells. Generation of high-affinity specific antibodies from less specific antibodies is carried out via a process called class switch recombination, where a mutator enzyme, activation-induced cytidine deaminase (AID) plays a key role by creating point mutations to immunoglobulin gene in B-cells.

The study revealed that outer membrane proteins HomA and HomB form a small β-barrel along with a surface exposed globular domain. Additionally, the interaction of HomB/HomA OMPs with B-cells transiently downregulates the expression of crucial enzyme AID and Ig switch germline transcription. Downregulation of AID leads to impairment of class switch recombination (CSR), resulting in significantly reduced switching to IgG and IgA antibodies.

Researchers also examined the immune-suppressive response of B-cells and observed that the cells stimulated with HomA/B show upregulation in the levels of IL10, IL35, as well as PDL1, a T-cell inhibition marker. These studies suggest the potential role of OMPs in immune response modulation strategies used by the pathogen to evade the immune response. The study provides a better understanding of H. pylori pathogenesis and assists in identifying novel targets for therapy.

This study is funded by the Indian Council of Medical Research (ICMR) and the Science and Engineering Research Board, Department of Science and Technology (DST), Govt of India.