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Evasion of the Immune System

Evasion of the immune system can occur by three main mechanisms: antigenic variation in the pathogen, the pathogen remaining dormant, and suppression of the immune response by the pathogen.

D. immitis thrives under a Th2 response because cytokines elicited as a result of the Th2-biased response are actually essential for growth and reproduction in helminthic parasites (Pastrana et al., 1998).

Parasitic nematodes produce moelcules that are homologous to immunoregulatory molecules in the host (Tezuka et al., 2003). IL-10 is a cytokine produced by Treg cells that suppresses Tcell responses.  D. immitis produces molecules that are analogous to host-derived molecules that stimulate IL-10 production (Simon et al., 2007).  By virtue of this mimicry, the parasite is able to control the T cell response through the supressesion of the functions of macrophages.

DiAg, a polyprotein produced by D. immitis, induces nonspecific IgE synthesis. IL-4, a product of T cell activation, induces class switching to IgE and supresses IFN-gamma production, which is known to inhibit IgE production. Thus, the parasite induces the host to produce large amounts of an antibody that is non-specific for the parasite itself (Tezuka et al., 2003). As a result, the humoral response is not an effective mechanism to allow for extermination of D. immitis. Parasitic nematodes such as D. immitis do secrete large amounts of products, but can live productively in their host for many years. It is assumed that some of these excretory-secretory products thus contribute to significant immuno-suppression (Tezuka et al. 2003).

DiAg prevents Th1-type immune responses. This is done through an IL-10 dependent mechanism that may result in an upregulation of a Th2 response. It has been found that Th2 responses are associated with parasite longevity (Tezuka et al., 2003). D. immitis preferentially elicits a Th2 type response. Stimulation of test subjects with antigens derived from D. immitis leads to increased populations of eosinophils and neutrophils (Simon et al., 2007).  Nematodes, a class to which D. immtis, belongs are advantaged by Th2 responses, leading to longer parasitic survival (Pastrana et al., 1998). Eosinophil cells counts are generally low in healthy individuals. 

Additionally, DiAg is a very stable molecule that is resistant to changes in temperature and extreme pH changes. The long-lasting presence of this immunomodulatory molecule in the host thus favors a lengthy life of D. immitis.

IL-10, a cytokine produced by Treg cells to suppress T cell responses, contrubutes to the evasion of the immune system by D. immitis (11). Permission pending from Dr. Flavio Salazar-Onfray.

Pastrana, Diana. 1998 Dec. Filarial Nematode Parasites Secrete a Homologue of the Human Cytokine Macrophage Migration Inhibitory Factor. Infection and Immunity: 5955 - 5963.

Simon, F. and L.H. Kramer. 2007. Immunopathology of Dirofilaria immitis infection. Veterinary research communications 21:161-171.

Tezuka, H. and Shinjiro Imai. 2003 July. Various types of Dirofilaria immitis Polyproteins selectively Induce a Th2-type Immune Response. Infection and Immunity 3802-3811.

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