Can mycotoxin exposure dysregulate immunity and lead to leukocytosis and EBV reactivation?

Mycotoxin exposure serves as a potent biological stressor that can substantially disrupt human immune homeostasis, leading to cellular suppression, localized or systemic inflammation, and the potential reactivation of latent viral pathogens.

Immunological and inflammatory mechanisms

• Cytokine dysregulation: In vitro and animal models demonstrate that mycotoxins, including ochratoxin A (OTA), aflatoxins, and trichothecenes, alter cytokine profiles and trigger the release of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-$\alpha$), interleukin-6 (IL-6), and interleukin-1beta (IL-$1\beta$).
• Cellular suppression: These toxins directly impair cellular immunity by reducing T-cell proliferation, viability, and macrophage activation, compromise mucosal barrier integrity, and can synergize with co-occurring bacterial endotoxins to amplify systemic inflammatory cascades.

Clinical markers of exposure and reactivation

• Leukocyte dynamics: The effect of mycotoxins on white blood cell counts is highly context-dependent; while chronic or high-dose toxicity typically leads to bone marrow suppression, lymphoid organ atrophy, and leukopenia, acute or transient leukocytosis can occur as a plausible secondary response to intense, localized inflammatory cytokine mobilization and mucosal barrier damage.
• Epstein-Barr Virus (EBV) reactivation: Maintaining EBV latency requires vigorous surveillance by CD4+ and CD8+ T-cells. Mycotoxin-induced suppression of cellular immunity impairs this viral control, enabling EBV to enter its active lytic cycle and express early lytic proteins such as early antigen (EA-D), which subsequently stimulates elevated EBV early antigen IgG titers. Experimental models confirm that aflatoxin B1 can disrupt EBV latency and enhance B-cell transformation.

Bottom line

• While experimental evidence firmly establishes that mycotoxins dysregulate immune cellular surveillance and can promote transient inflammatory leukocytosis and EBV reactivation, direct human epidemiological studies correlating quantified environmental mycotoxin exposure with elevated EBV early antigen IgG titers remain limited.