The impact of Fusarium mycotoxins on human and animal host susceptibility to infectious diseases

Abstract

Contamination of food and feed with mycotoxins is a worldwide problem. At present, acute mycotoxicosis caused by high doses is rare in humans and animals. Ingestion of low to moderate amounts of Fusarium mycotoxins is common and generally does not result in obvious intoxication. However, these low amounts may impair intestinal health, immune function and/or pathogen fitness, resulting in altered host pathogen interactions and thus a different outcome of infection. This review summarizes the current state of knowledge about the impact of Fusarium mycotoxin exposure on human and animal host susceptibility to infectious diseases. On the one hand, exposure to deoxynivalenol and other Fusarium mycotoxins generally exacerbates infections with parasites, bacteria and viruses across a wide range of animal host species. Well-known examples include coccidiosis in poultry, salmonellosis in pigs and mice, colibacillosis in pigs, necrotic enteritis in poultry, enteric septicemia of catfish, swine respiratory disease, aspergillosis in poultry and rabbits, reovirus infection in mice and Porcine Reproductive and Respiratory Syndrome Virus infection in pigs. However, on the other hand, T-2 toxin has been shown to markedly decrease the colonization capacity of Salmonella in the pig intestine. Although the impact of the exposure of humans to Fusarium toxins on infectious diseases is less well known, extrapolation from animal models suggests possible exacerbation of, for instance, colibacillosis and salmonellosis in humans, as well.

Figure 1

The effect of Fusarium mycotoxins on the intestinal epithelium. A variety of Fusarium mycotoxins alter the different intestinal defense mechanisms including epithelial integrity, cell proliferation, mucus layer, immunoglobulins (Ig) and cytokine production. (IEC: intestinal epithelial cell) (based on [9]).

Figure 2

The impact of deoxynivalenol and T-2 toxin on a Salmonella Typhimurium infection in pigs. In vitro, deoxynivalenol (DON) and T-2 toxin (T-2) promote Salmonella invasion (1) and transepithelial passage (2) of IPEC-J2 cell layer. Subsequently, the bacterium can spread to the bloodstream using the host macrophage to establish the systemic infection. In vitro, DON and T-2 enhance Salmonella uptake (3) in porcine alveolar macrophages. The Salmonella invasion of macrophages coincides with membrane ruffling, caused by actin cytoskeletal changes. Activation of host Rho GTPases by the Salmonella pathogenicity island (SPI)-1 type 3 secretion system (T3SS) effector proteins SopB, SopE, SopE2 and SopD leads to actin cytoskeleton reorganization. After Salmonella internalization has occurred, the bacterium injects the effector protein SptP which promotes the inactivation of Rho GTPases. The bacterium can also modulate the actin dynamics of the host cell in a direct manner through the bacterial effector proteins SipA and SipC. The mycotoxin DON enhances the uptake of Salmonella in macrophages through activation of the mitogen-activated protein kinases (MAPK) extracellular signal-regulated kinases (ERK1/2) pathway, which induces actin reorganizations and membrane ruffles. DON and T-2 do not affect intracellular bacterial proliferation (4) (based on [41,44]).