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How Mold Triggers the Immune System

Mold-exposure causes allergy, infection, and toxicity. But in my clinical practice, I observe a far more common problem—a form of massive inflammation called innate immune activation.

In the medical-legal arena, the inflammatory potential of indoor air pollution is hotly contested. But a closer look at the immune system reveals that it has specific detectors to identify and respond to mold particles, a finding that proves that the human body is vulnerable to inflammation from mold.

In this article, I will discuss how the immune system uses sensors known as Pattern Recognition Receptors (PRRs) to set off an inflammatory cascade.

PRRs — Immune Sensors to Detect Danger

Proteins on your immune cells can detect microbes and damaged cells. These detectors are called Pattern Recognition Receptors, or PRRs. These PRRs are found throughout your body, including lung cells, known as the epithelium, which have direct contact to the air and the particles within it.

PRRs are found inside your immune cell on the outer wall of the cell (cell membrane), packages inside the cell (endosome membranes), and within the cell fluid (cytosol). PRRs are also found outside the cell—in the bloodstream and in the interstitial fluid found in tissues outside of blood vessels.

There are four major families of PRRs, including toll-like receptor. Each family is evolved to detect different molecular signals that will set it on high alert.

PAMPs — Signals of a Foreign Invader

Operating at the level of the cell, the PRRs are the immune system’s sentinels. The PRRs detect the unwanted intruder by binding tomolecular signals from mold, bacteria, viruses, and parasites. These triggering non-self molecular signals are known as Pathogen Associated Molecular Patterns, or PAMPs.

When the PAMPs from an invading microbe binds the PRRs, an immune response begins. The goal of this immune response is to generate inflammation and other changes within the body that kill the microbe, which prevents infection, and neutralize other harms.

But if this immune response becomes excessive, as can happen with chronic exposure to indoor air pollution, the inflammatory response devolves from a protective process (that prevents infection) to a harmful one that damages tissues and weakens the immune system.

DAMPs — Signals of Damage

Within the body, microbial warfare is a messy affair.

The damage—to both invading microbes and to host tissues—results in the release of damage molecules. The danger molecules are known as Damage Associated Molecular Patterns, or DAMPs. The DAMPs trigger the PRRs, which stimulates further cell death and other immune responses.

DAMPs serve to signal ongoing damage within the body, keeping the immune system alert and active. Though both PAMPs and DAMPs trigger the immune system—by binding to PRRs—the distinction is PAMPs are present in invading microbes and DAMPs are present in damaged microbes, as well as damaged host cells.

Fungal PAMPs and DAMPs — Proof Positive that Mold Exposure is Inflammatory

Mold causes innate immune activation because there are fungal PAMPs and DAMPs.

Fungal cells walls are composed of sugar molecules that are PAMPs. The three most prevalent PAMPs are beta-glucans, mannans, and chitins. To give one example dectin-1, a PRR, is found on lung cells where they can be triggered by inhaled mold particles.  Moreover, metabolic products made by mold act as PAMPs and allergens—proteins, enzymes, and toxins can trigger inflammation, toxicity, and changes in gene responses.

As the authors of one study wrote,

“The bottom line is that fungal exposures can through a panoply of mechanisms result in inflammation.”

Theinflammasome is a part of the innate immune system that, when triggered, causes inflammation. The inflammasome can be activated by every class of microbe. The main inflammasome associated with mold is known as NLRP3. The NLRP3 inflammasome is activated by exposure to fungal PAMPs, particularly beta-glucans. Beta-glucans, the main type of sugar particle within the mold cell wall, stimulates dectin-1.

Though the inflammasome is intended to protect the body, it can cause an intense and detrimental inflammatory response when overstimulated—as occurs with chronic respiratory exposure to indoor mold and other pollutants within a water-damaged building.

References

Amarante-Mendes, Gustavo P., et al. “Pattern recognition receptors and the host cell death molecular machinery.” Frontiers in immunology 9 (2018): 2379.

Williams, P. Brock, et al. “Innate and adaptive immune response to fungal products and allergens.” The Journal of Allergy and Clinical Immunology: In Practice4.3 (2016): 386-395.

Tavares AH, Bürgel PH, Bocca AL (2015) Turning Up the Heat: Inflammasome Activation by Fungal Pathogens. PLoS Pathog 11(7): e1004948.