Fungal Toxins: The Modulation of Host Immunity

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Research suggests that fungal toxins like mycotoxins are produced during active fungi infections in humans and experimental models. The human body possesses innate and adaptive immune recognition that eliminates invading pathogens from the host’s body. Imbalances in immune responses usually facilitate microbial infection. 

Fungi are widespread organisms that thrive in various natural environments such as soils, animals, plants, and the human body. Fungi grow in the presence of warmth, humility, and moisture. The types of fungi that grow on crops and harvested foodstuffs produce mycotoxins which harm health.

Although there is a wide range of toxic effects of toxins in human health, the understanding of toxin-mediated modulation in the immune response is still shallow. Let’s look at how the current understanding of fungal toxins contributes to host immunity modulation.

A detailed review of fungal toxins

Mycotoxins are classified as natural secondary metabolites produced by fungi. They grow on various agricultural products such as cereals, grains, nuts, spices, apples, dried fruits, and coffee beans. Around 20-25% of food crops worldwide contain mycotoxin contamination. Additionally, mycotoxin and mycotoxin-producing fungi are frequently found in construction materials and air samples from water-damaged buildings.

The gut is the first point of contact when myotoxins are first ingested in the host’s system. The gastrointestinal mucosa (GIM) comprises epithelial cells connected in phases by desmosomes, tight junctions, and adherence junctions. The GIM has a diverse colony of bacteria, archaea, and eukarya that help maintain general health maintenance. The GIM layer restricts the movement of microbes and toxic substances from the gastrointestinal lumen into the systemic compartment.

Myotoxins influences the gastrointestinal microbiota directly. This influence happens through a secondary mechanism that involves releasing antimicrobial compounds from host cells damaged by myotoxin. Additionally, the microbiota can influence the biological components of ingested mycotoxins and the metabolites associated with them.

The body can detoxify mycotoxins through biotransformation. Additionally, the body can physically prevent the absorption of mycotoxins across the gut. The primary routes of mycotoxin absorption are ingestion and inhalation. Furthermore, Some mycotoxins and peptide/protein toxins contribute to fungal infection and pathogenicity.

These fungal infections are the leading cause of mortality and morbidity worldwide. According to Brown et al., they are estimated to cause 1.5 million deaths per year. Some of the predisposing factors for the development of life-threatening systemic infections include gastrointestinal surgery and immunosuppressive therapy.

Let’s explore the impact of mycotoxins, peptides, and protein toxins on hosts’ immune defense modulation.

Gliotoxin 

Gliotoxin is a class of epipolythiodioxiopiperazine (ETP) toxins. A fungus closely associated with gliotoxin, A. fumigatus, causes life-threatening respiratory and systemic infections in patients with compromised immunity. Gliotoxin also causes the cytoskeletal remodeling of alveolar epithelial cells in humans.

Gliotoxin can induce apoptosis and cytoskeletal changes that affect macrophage function. It also affects cytokine expression and releases from macrophages. Cytokines are molecules that coordinate immune responses.

Aflatoxins 

Aflatoxins are coumarin ring-containing carcinogens from polyketides. Aflatoxins significantly affect epithelial cell barriers negatively. It also reduces the ability of human monocytes to phagocytose and kill candida Albicans. 

Additionally, aflatoxin negatively affects the phagocytosis of Escherichia coli by monocytes. Human neutrophils are also affected by aflatoxin through the depletion of intracellular ATP and the increase of apoptosis.

Ochratoxin

Ochratoxin significantly affects the functioning of the gastrointestinal barrier by stimulating apoptosis. Additionally, it impairs the chemotactic activity of peritoneal macrophages. 

Ochratoxin can also increase oxidative damage to parenchyma organs and neutrophil infiltration into the duodenum. This class of toxins also causes both immunosuppression and pro-inflammatory responses.

Fumonisin

Fumonisin causes an inhibitory effect on livestock macrophages. It also causes prolonged intestinal infection and the impairment of intestinal antigen-presenting cells in dendritic cells.

Conclusion

The elimination of infectious microbes from the body is dependent on the innate and adaptive immunity of the host. Both the body’s mucosal barriers and immune cells protect underlying tissues from pathogenic attacks. They also play a crucial role in microbial recognition and defense. As seen in the information above, most mycotoxins affect mucosal barriers’ structural functioning and suppress cellular immunity.

The above information also shows that toxin-mediated alterations in innate and adaptive host defenses increase susceptibility to infections by pathobionts present in the resident microbiota. As illustrated at the beginning of this article, little is known about fungal toxins and health; therefore, there is a need for more extensive research on these toxins to curb their adverse health effects.

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