Immunity and immune modulation inTrypanosoma cruziinfection

Abstract

Chagas disease is caused by the protozoan Trypanosoma cruzi. The parasite reaches the secondary lymphoid organs, the heart, skeletal muscles, neurons in the intestine and esophagus among other tissues. The disease is characterized by mega syndromes, which may affect the esophagus, the colon and the heart, in about 30% of infected people. The clinical manifestations associated with T. cruzi infection during the chronic phase of the disease are dependent on complex interactions between the parasite and the host tissues, particularly the lymphoid system that may either result in a balanced relationship with no disease or in an unbalanced relationship that follows an inflammatory response to parasite antigens and associated tissues in some of the host organs and/or by an autoimmune response to host antigens. This review discusses the findings that support the notion of an integrated immune response, considering the innate and adaptive arms of the immune system in the control of parasite numbers and also the mechanisms proposed to regulate the immune response in order to tolerate the remaining parasite load, during the chronic phase of infection. This knowledge is fundamental to the understanding of the disease progression and is essential for the development of novel therapies and vaccine strategies.

The Interleukin-17 (IL-17) puzzle in Chagas disease

“…The acute phase is characterized by the presence of the parasite in the bloodstream [4] . During the acute phase, an effective immune response is settled to control parasite replication in the tissues [5] . NK, T, and B cells are crucial to mediate parasite clearance through the production of interferon-γ, interleukin-17 and specific antibodies [4][5][6][7] .…”

“…During the acute phase, an effective immune response is settled to control parasite replication in the tissues [5] . NK, T, and B cells are crucial to mediate parasite clearance through the production of interferon-γ, interleukin-17 and specific antibodies [4][5][6][7] . Immunity cannot sterilize the host, thus leading to infection persistence and therefore, a chronic disease [5] .…”

“…NK, T, and B cells are crucial to mediate parasite clearance through the production of interferon-γ, interleukin-17 and specific antibodies [4][5][6][7] . Immunity cannot sterilize the host, thus leading to infection persistence and therefore, a chronic disease [5] . The chronic illness affects mainly the heart, esophagus and large intestine [2] .…”

“…The genesis of the chronic inflammatory reaction is debatable. It may be induced by the persistence of the parasite in the tissues, due to an inadequate immune response or an exaggerated response as a result of missing regulatory mechanisms as an autoimmune disease [5] . Trypanocidal drug-treatment, during the chronic phase, diminishes the parasite load but was unable to revert or to halt the development of the cardiac pathology [9] , arguing that myocardial damage may be independent of the parasite [10] .…”

“…These results are in agreement with the postulated role for IL-17 as an inflammatory cytokine [13][14][15] . On the other hand, there is evidence that IL-17 may regulate Th1 responses or recruits IL-10 neutrophil producers, favoring host survival during the acute infection by the down-regulation of an exacerbated immune response [5,16,17] . Experimental evidence concerning the role of IL-17 during the chronic phase of T. cruzi infection is missed.…”