Induction of cell-mediated immunity during early stages of infection with intracellular protozoa

Abstract

Toxoplasma gondii and Trypanosoma cruzi are intracellular parasites which, as part of their life cycle, induce a potent cell-mediated immunity (CMI) maintained by Th1 lymphocytes and IFN-γ. In both cases, induction of a strong CMI is thought to protect the host against rapid parasite multiplication and consequent pathology and lethality during the acute phase of infection. However, the parasitic infection is not eliminated by the immune system and the vertebrate host serves as a parasite reservoir. In contrast, Leishmania sp, which is a slow growing parasite, appears to evade induction of CMI during early stages of infection as a strategy for surviving in a hostile environment (i.e., inside the macrophages which are their obligatory niche in the vertebrate host). Recent reports show that the initiation of IL-12 synthesis by macrophages during these parasitic infections is a key event in regulating CMI and disease outcome. The studies reviewed here indicate that activation/inhibition of distinct signaling pathways and certain macrophage functions by intracellular protozoa are important events in inducing/modulating the immune response of their vertebrate hosts, allowing parasite and host survival and therefore maintaining parasite life cycles.

Update on Chagas' disease in Mexico

“…However, additional studies are necessary and it will be some time before new treatments become available. Vaccines are still out of reach, even though a great amount of research has allowed a better understanding of the immune mechanisms of the infection, 25,26 and proved that the development of a vaccine is clearly possible.…”

Macrophage Migration Inhibitory Factor Contributes to Host Defense against AcuteTrypanosoma cruziInfection

“…The parasite plays a fundamental role in inducing immunopathology and tissue damage in organs such as the heart, esophagus, and colon by sequentially inducing inflammatory responses, cellular lesions, and fibrosis (60). Host resistance in experimental acute T. cruzi infection is dependent on both innate and acquired immune responses mediated by macrophages, natural killer (NK) cells, CD4 ϩ T cells, CD8 ϩ T cells, and B cells (17,31,33). Proinflammatory cytokines, such as interleukin-12 (IL-12), tumor necrosis factor alpha (TNF-␣), and gamma interferon (IFN-␥), also play a critical role in protective immunity against T. cruzi (40,44,48,59), since genetically engineered mice lacking any of these cytokines fail to control parasitemia and rapidly succumb to infection.…”

Protection against Toxoplasmosis in Mice Immunized with Different Antigens of Toxoplasma gondii Incorporated into Liposomes

“…Antibodies have been shown to transfer protection passively (Johnson et al 1983). There is also evidence that protective immunity against toxoplasmosis can be mediated by CD8 and CD4 lymphocytes (Gazzinelli et al 1998). Thus, an adjuvant that promotes activation of these Tcell subsets would theoretically be an ideal component of a T. gondii vaccine.…”