Hepatocarcinogenesis is linked to environmental factors, with microplastics (MPs) emerging as a global environmental concern that may contribute to liver injury. However, the impact of MPs on the early stages of hepatocarcinogenesis has been largely ignored. Here we investigated the impact of long-term MP exposure on the formation of preneoplastic lesions during hepatocarcinogenesis induced by diethylnitrosamine (DEN) in rats. Rats were injected with DEN to induce preneoplastic lesions, and then they were orally administered with 1 µm MPs 0.5 mg/kg body weight per day for 20 weeks. The results revealed that long-term exposure to MPs did not induce the formation of glutathione S-transferase placental form (GST-P)-positive foci as preneoplastic lesions during hepatocarcinogenesis in these animals, thereby indicating non-carcinogenicity. However, MP exposure resulted in a 1-fold increase in both the number and size of GST-P-positive foci in rats initiated with DEN compared to those treated with DEN alone. Accordingly, MP exposure led to a 0.61-fold increase in the index of proliferating cell nuclear antigen (PCNA)-positive cells in DEN-initiated rats when compared to DEN treatment alone. In addition, the composition of the gut microbiota was significantly altered, accompanied by various levels of short-chain fatty acids. Our results suggest that long-term MP exposure can promote pre-neoplastic lesion formation in DEN-induced rats by increased cell proliferation as well as alterations in the gut microbiota and short-chain fatty acid levels. This highlights the potential health risks associated with hepatocarcinogenesis linked to long-term exposure to MPs.

Cellular-mediated immunity against invasive fungal infections is fundamentally governed by Major Histocompatibility Complex (MHC) restriction, whereby T cells detect fungal invasion indirectly through peptide fragments displayed on host MHC molecules rather than by recognizing intact fungal pathogens. In contrast to B cells, which bind native microbial antigens, T lymphocytes monitor antigen-presenting cells for processed fungal peptides presented by MHC class I and class II molecules. This review examines the molecular mechanisms underlying fungal antigen processing and presentation, emphasizing the pivotal contributions of MHC class II-restricted CD4 T-helper (TH1/TH17) cells and cross-presented, MHC class I-restricted CD8 cytotoxic T lymphocytes to antifungal host defense. We also summarize key experimental approaches, including overlapping peptide libraries, ELISpot assays, and peptide–MHC multimers, for defining MHC function and identifying immunodominant fungal antigenic determinants. Evidence from representative pathogenic fungal antigens, including Asp f16, Crf1, Eng2, and the multivalent rCpa1 vaccine, highlights both the promise and complexity of achieving cross-protective cellular immunity. Importantly, amino acid sequence similarity alone is insufficient to predict T-cell cross-reactivity, indicating that computational prediction and experimental epitope mapping should be employed as complementary approaches for the accurate identification and validation of immunologically relevant epitopes. Finally, elucidating the molecular principles governing fungal peptide presentation establishes a rational foundation for the development of broadly protective epitope-based vaccines and next-generation immunotherapeutic strategies.