Helicobacter pylori enhances HLA-C expression in the human gastric adenocarcinoma cells AGS and can protect them from the cytotoxicity of natural killer cells
Etikala Apoorva
CSIR-Centre for Cellular and Molecular Biology, Hyderabad, Telangana, India
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
Search for more papers by this authorRini Jacob
CSIR-Centre for Cellular and Molecular Biology, Hyderabad, Telangana, India
Search for more papers by this authorDesirazu N. Rao
Department of Biochemistry, Indian Institute of Science, Bangalore, India
Search for more papers by this authorCorresponding Author
Santosh Kumar
CSIR-Centre for Cellular and Molecular Biology, Hyderabad, Telangana, India
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
Correspondence
Santosh Kumar, CSIR-Centre for Cellular and Molecular Biology, Habsiguda, Uppal Road, Hyderabad, Telangana 500007, India.
Email: skumar@ccmb.res.in
Search for more papers by this authorEtikala Apoorva
CSIR-Centre for Cellular and Molecular Biology, Hyderabad, Telangana, India
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
Search for more papers by this authorRini Jacob
CSIR-Centre for Cellular and Molecular Biology, Hyderabad, Telangana, India
Search for more papers by this authorDesirazu N. Rao
Department of Biochemistry, Indian Institute of Science, Bangalore, India
Search for more papers by this authorCorresponding Author
Santosh Kumar
CSIR-Centre for Cellular and Molecular Biology, Hyderabad, Telangana, India
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
Correspondence
Santosh Kumar, CSIR-Centre for Cellular and Molecular Biology, Habsiguda, Uppal Road, Hyderabad, Telangana 500007, India.
Email: skumar@ccmb.res.in
Search for more papers by this authorAbstract
Helicobacter pylori (H. pylori) seems to play causative roles in gastric cancers. H. pylori has also been detected in established gastric cancers. How the presence of H. pylori modulates immune response to the cancer is unclear. The cytotoxicity of natural killer (NK) cells, toward infected or malignant cells, is controlled by the repertoire of activating and inhibitory receptors expressed on their surface. Here, we studied H. pylori-induced changes in the expression of ligands, of activating and inhibitory receptors of NK cells, in the gastric adenocarcinoma AGS cells, and their impacts on NK cell responses. AGS cells lacked or had low surface expression of the class I major histocompatibility complex (MHC-I) molecules HLA-E and HLA-C—ligands of the major NK cell inhibitory receptors NKG2A and killer-cell Ig-like receptor (KIR), respectively. However, AGS cells had high surface expression of ligands of activating receptors DNAM-1 and CD2, and of the adhesion molecules LFA-1. Consistently, AGS cells were sensitive to killing by NK cells despite the expression of inhibitory KIR on NK cells. Furthermore, H. pylori enhanced HLA-C surface expression on AGS cells. H. pylori infection enhanced HLA-C protein synthesis, which could explain H. pylori-induced HLA-C surface expression. H. pylori infection enhanced HLA-C surface expression also in the hepatoma Huh7 and HepG2 cells. Furthermore, H. pylori-induced HLA-C surface expression on AGS cells promoted inhibition of NK cells by KIR, and thereby protected AGS cells from NK cell cytotoxicity. These results suggest that H. pylori enhances HLA-C expression in host cells and protects them from the cytotoxic attack of NK cells expressing HLA-C-specific inhibitory receptors.
CONFLICT OF INTEREST STATEMENT
We declare that there is no conflict of interest.
Open Research
DATA AVAILABILITY STATEMENT
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