How do helminthic infections alter the immune system?

Edward Mitre, M.D.
assistant professor
Uniformed Services University

Meseret Belayneh, ET

How do helminthic infections alter the immune system?

Edward Mitre
assistant professor,
F. Edward Hebert School of Medicine,
Uniformed Services University

This is a great question, because the immune response that develops toward worms (helminths) is very different from the response toward other infectious agents such as viruses, bacteria, and fungi. Worm infections induce an immune response similar to that found in allergic diseases, with production of eosinophils (a type of white blood cell) and IgE (a type of antibody). This response frequently causes allergic symptoms such as hives and itching, especially in the first months of infection and in settings of reinfection. The allergic symptoms occur in part because white blood cells called mast cells and basophils release histamine and other inflammatory substances when IgE antibodies on their cell surfaces bind worms or worm products.

The arm of the immune system responsible for developing increased numbers of eosinophils and IgE is called a type 2 immune response. In this response, helper CD4+ T cells, specialized white blood cells that help coordinate immune responses, release molecules called interleukins (IL) that tell other immune system cells what to do. Type 2 helper CD4+ T cells release IL-4, IL-5, and IL-13. IL-4 and IL-13 direct antibody-producing white blood cells (B cells) to make IgE, and IL-5 increases production of eosinophils from the bone marrow. Understanding how type 2 immune responses develop is an area of active investigation, and it is clear that this response is a complicated one that involves many other cell types in addition to those mentioned. Indeed, in just the past few years several additional cell types have been identified that may be essential for starting type 2 immune responses.

The type 2 immune response that develops after infection with worms is somewhat protective, as disruption of this response typically results in moderate increases in worm numbers in experimental infections. While the mechanism by which the type 2 response fights off worm infections isn’t completely understood, some aspects are known. For example, molecules released from eosinophils are directly toxic to worms. Additionally, when worms parasitize the intestines, type 2 responses cause rapid turnover of the cells that line the intestinal tract, increased mucus production in the intestinal lining, and increased contractions of the intestines. These responses help the body mechanically resist worm infections in the intestines. Despite these effects, we know that type 2 responses are not completely protective against worms because most successful parasitic worms persist in people for years despite the development of a strong type 2 immune response. Further, unlike chickenpox and measles, prior infection with parasitic worms does not prevent the development of future infections. For this reason, children in areas that are highly endemic for intestinal worm infections need to be treated several times a year for repeated infections. This lack of natural immunity after a worm infection is one reason why we do not have a vaccine against worm infections in people.

Interestingly, when a person is infected with worms for a very long time, the immune response to the worms starts to turn off. This downregulation of the immune response is due in part to an increase in some of the body’s natural “brakes” on the immune system. These brakes include soluble proteins such as IL-10 and TGFβ and specialized white blood cells called regulatory T cells. These brakes have suppressive effects on a number of immune cells, and their upregulation during chronic worm infection is associated with a decrease in the allergic symptoms caused by worms. In addition to decreasing some symptoms caused by worms, these brakes may also help protect against allergy and autoimmune diseases (diseases such as lupus and rheumatoid arthritis in which the immune system attacks a person’s own body). Animal studies of allergy and autoimmune disease have shown parasitic worms to have a beneficial effect, and a clinical trial infecting people with parasitic worms showed that the symptoms of inflammatory bowel disease diminished. Currently, researchers are trying to better understand how worms protect against allergy and autoimmune diseases to gain insights for developing therapies against these diseases. Additionally, some investigators are evaluating the feasibility of using actual worms as therapy for certain diseases.