Immunomodulatory potential of Alternaria mycotoxins on immune and intestinal cells: a comparative systematic in vitro study

Alternaria species produce structurally diverse mycotoxins that frequently contaminate food and are discussed in association with adverse health effects. However, systematic knowledge of their immunosuppressive potential is limited. This study evaluated seven Alternaria mycotoxins-alternariol (AOH), alternariol monomethyl ether (AME), altenuene (ALT), alterperylenol (ALTP), altertoxin I (ATX-I), altersetin (AST), and tentoxin (TEN)-in immune and intestinal cells. NF-κB reporter gene assays were performed in THP-1 monocytes and phorbol 12-myristate 13-acetate-differentiated macrophages (0.01-25 µM), while cytokine transcription and secretion (IL-6, IL-8, IL-10, TNF-α) were analyzed in Caco-2 and HCEC-1CT cells (0.1–30 µM) applying qRT-PCR and ELISA. All mycotoxins suppressed NF-κB activation in immune cells, though with differing potency. AOH, ALTP, and ATX-I were active at concentrations ≥ 1 µM in both models. AME and AST were more potent in macrophages (≥ 0.01 µM) than monocytes (≥ 5 µM). TEN suppressed the pathway at ≥ 0.1 µM in macrophages and ≥ 5 µM in monocytes, while ALT at ≥ 5 µM in both cell types. In intestinal models, AOH, AME, ALTP, ATX-I, and TEN modulated cytokine transcription, with stronger responses in non-tumorigenic HCEC-1CT cells. ALTP emerged as the most potent immunosuppressive compound, reducing IL-6, IL-8, and/or TNF-α secretion at concentrations ≥ 0.1 µM. AOH showed dual activity, suppressing IL-6/IL-8 at 30 µM, while modulating TNF-α in a cell-type-dependent manner (increased secretion in Caco-2, decreased in HCEC-1CT). This comparative study reveals immunosuppressive profiles of Alternaria mycotoxins in immune and epithelial cells, highlighting their relevance as food contaminants capable of modulating both intestinal and systemic immune responses.