NIH R01 · 2025
Role of the p53 P47S mutation in influencing prevalence and immune response to H. pylori
We discovered that a human TP53 gene variant at amino acid 47 codes for a “hypomorphic” p53 protein. This hypomorph p53 variant (P47S) retains most but not all of its functions and has been linked to changes in innate and adaptive immunity. Macrophages containing the P47S variant are defective in ferroptosis, M2 polarized, and show more productive infections by H. pylori (Hp) and other bacteria. Macrophage adaptive response is essential for eliminating Hp infection and is suppressed in chronic infections that lead to gastritis. Unbiased WT and P47S macrophage proteomics revealed marked differences in Liver X Receptor activation, arginase II activity, inflammation, iron transport, and…
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