The relationship between parasites and autoimmune disease is intricate, involving mechanisms that can lead to both tissue damage and immune protection. An autoimmune disease occurs when the body’s immune system mistakenly identifies its own healthy tissues as foreign and attacks them, causing chronic inflammation. Parasites are organisms that live on or in a host, drawing nutrients from it. They are broadly categorized into single-celled protozoa and larger, multicellular helminths (worms). These infections trigger an immune response that can sometimes become misdirected against the host’s own cells.
The Theory Behind the Connection
The dramatic increase in autoimmune diseases and allergies in industrialized nations led to the development of the “Hygiene Hypothesis.” This hypothesis suggested that reduced exposure to common childhood infections resulted in an improperly “tuned” immune system, predisposing individuals to inflammatory disorders. This idea was later refined into the “Old Friends Hypothesis” to focus on a more specific group of organisms.
The “Old Friends Hypothesis” posits that the immune system co-evolved with persistent, tolerated organisms like certain bacteria and helminths. These ancient co-inhabitants provided constant immunoregulatory signals necessary for the immune system to dampen inflammation and maintain tolerance. Modern environments, characterized by improved sanitation, have depleted these essential regulatory stimuli, creating an evolutionary mismatch. This lack of exposure results in a dysregulated immune system that attacks self-tissues, explaining the surge in chronic inflammatory conditions.
How Parasites Can Trigger Autoimmunity
While the decline of infections is linked to rising autoimmune rates, the presence of other parasites can directly trigger an autoimmune response, primarily through molecular mimicry. This occurs when an antigen (a specific protein) on the parasite structurally resembles a protein found on the host’s own cells. The immune response is initially directed at the parasite antigen, but the resulting antibodies or T-cells mistakenly cross-react with the similar self-protein, initiating tissue damage.
A classic example is the protozoan Trypanosoma cruzi, which causes Chagas disease. Antigens from this parasite can mimic proteins found in human heart and nerve tissue. This molecular mimicry leads to an autoimmune attack on the heart muscle, resulting in chronic cardiac issues.
Bystander Activation
Another mechanism is bystander activation, a consequence of intense inflammation caused by the parasite. When the immune system launches a massive inflammatory response, local damage releases previously hidden host proteins, called self-antigens, into the environment. Inflammatory cytokines released during the fight can non-specifically activate self-reactive T-cells that were previously dormant. This surge of inflammatory mediators pushes the immune system toward a full-blown autoimmune attack.
How Parasites Can Suppress Autoimmunity
Despite their potential to trigger autoimmunity, many parasites, particularly helminths like hookworms, actively suppress the host’s immune response. This immunomodulation is a survival strategy, allowing the parasite to establish a long-term, chronic infection without being expelled. This self-serving down-regulation coincidentally benefits the host by dampening autoimmune inflammation.
The central mechanism involves shifting the host’s immune profile away from pro-inflammatory Th1 and Th17 responses, which are associated with autoimmune conditions, toward a regulatory Th2 response. Parasite-derived molecules stimulate the generation and activity of Regulatory T-cells (Tregs). Tregs are specialized white blood cells that actively suppress generalized inflammation and maintain immune tolerance.
These regulatory cells and the parasites release powerful anti-inflammatory cytokines, especially Interleukin-10 (IL-10) and Transforming Growth Factor-beta (TGF-beta). IL-10 inhibits the function of antigen-presenting cells and T-cells, putting a brake on the inflammatory cascade. TGF-beta aids in the differentiation of Tregs and promotes tissue repair, reducing the chronic inflammation seen in autoimmune diseases.
Using Parasites in Treatment
The powerful immunoregulatory effects of helminth infections have led to the exploration of “Helminthic Therapy,” or “worm therapy,” as an experimental treatment for autoimmune conditions. This therapy involves the intentional introduction of specific, non-pathogenic helminth species or their eggs, such as the human hookworm, into a patient. The goal is to harness the parasite’s natural ability to stimulate a protective, anti-inflammatory immune environment.
Clinical trials have investigated this approach for diseases like Crohn’s disease, ulcerative colitis, and multiple sclerosis, showing positive results in symptom alleviation. However, the use of live organisms carries inherent risks and is not yet a widely approved medical treatment due to safety and regulatory issues.
The current direction of research focuses on isolating the specific immunomodulatory molecules that the parasites excrete. Scientists are working to identify and synthesize these parasite-derived molecules, such as proteins responsible for stimulating Tregs and inducing IL-10 production. The ultimate aim is to develop a safe, pill-based immunotherapy that delivers the therapeutic benefit of the parasite’s regulatory signals without requiring a live infection.