Effect of Penicillium mycotoxins on the cytokine gene expression, reactive oxygen species production, and phagocytosis of bovine macrophage (BoMacs) function

• Penicillium mycotoxins (PMs) have a potential immunotoxicity on macrophages.
• PMs differentially altered cytokine gene expression of BoMacs.
• Patulin and penicillic acid decreased reactive oxygen species and phagocytosis.
• Ochratoxin A induced the percent phagocytosis of MAP at 6.25 and 12.5 μM.
• Sub-lethal concentrations of PMs can affect macrophage function.

Bovine macrophages (BoMacs) were exposed to the following Penicillium mycotoxins (PM): citrinin (CIT), ochratoxin A (OTA), patulin (PAT), mycophenolic acid (MPA) and penicillic acid (PA). PM exposure at the concentration that inhibits proliferation by 25% (IC25) differentially for 24 h altered the gene expression of various cytokines. OTA significantly induced IL-1α expression (p < 0.05), while the expression of IL-6 was suppressed (p < 0.01). MPA significantly induced the expression of IL-1α (p < 0.05) and reduced the expression of IL-12α (p < 0.01) and IL-10 (p < 0.01). PAT significantly suppressed the expression of IL-23 (p < 0.01), IL-10 (p < 0.05) and TGF-β (p < 0.05). Some PMs also affected reactive oxygen species (ROS) and phagocytosis of Mycobacterium avium ssp. Paratuberculosis (MAP) at higher concentrations. PAT and PA for example, significantly decreased the percent phagocytosis of MAP at 5.0 (p < 0.01) and 15.6 μM (p < 0.01), respectively, but only PA significantly suppressed PAM-3-stimulated ROS production at 62.5 (p < 0.05) and 250.0 μM (p < 0.01). OTA significantly increased the percent phagocytosis of MAP at 6.3 (p < 0.05) and 12.5 μM (p < 0.01). These findings suggest that exposure to sub-lethal concentrations of PMs can affect macrophage function, which could affect immunoregulation and innate disease resistance to pathogens.