Immunity and immunosuppression in experimental visceral leishmaniasis

Abstract

Leishmaniasis is a disease caused by protozoa of the genus Leishmania, and visceral leishmaniasis is a form in which the inner organs are affected. Since knowledge about immunity in experimental visceral leishmaniasis is poor, we present here a review on immunity and immunosuppression in experimental visceral leishmaniasis in mouse and hamster models. We show the complexity of the mechanisms involved and differences when compared with the cutaneous form of leishmaniasis. Resistance in visceral leishmaniasis involves both CD4 + and CD8 + T cells, and interleukin (IL)-2, interferon (IFN)-γ, and IL-12, the latter in a mechanism independent of IFN-γ and linked to transforming growth factor (TGF)-ß production. Susceptibility involves IL-10 but not IL-4, and B cells. In immune animals, upon reinfection, the elements involved in resistance are different, i.e., CD8 + T cells and IL-2. Since one of the immunopathological consequences of active visceral leishmaniasis in humans is suppression of T-cell responses, many studies have been conducted using experimental models. Immunosuppression is mainly Leishmania antigen specific, and T cells, Th2 cells and adherent antigen-presenting cells have been shown to be involved. Interactions of the co-stimulatory molecule family B7-CTLA-4 leading to increased level of TGF-ß as well as apoptosis of CD4 + T cells and inhibition of macrophage apoptosis by Leishmania infection are other components participating in immunosuppression. A better understanding of this complex immune response and the mechanisms of immunosuppression in experimental visceral leishmaniasis will contribute to the study of human disease and to vaccine development.

Cytokines and visceral leishmaniasis: a comparison of plasma cytokine profiles between the clinical forms of visceral leishmaniasis

“…Here, a mixed cytokine profile (Th1 and Th2) was detected in the patients with the active disease. This mixed profile has also been reported by other investigators (Goto & Lindoso 2004, Peruhype-Magalhães et al 2005, Goto & Prianti 2009). The increase in inflammatory cytokines could be associated with the physiopathological alterations seen during the active disease, whereas the production of IL-10 has been suggested to be important for the survival and persistence of the parasite inside macrophages (PeruhypeMagalhães et al 2006.…”

Immunogenicity in dogs of three recombinant antigens (TSA, LeIF and LmSTI1) potential vaccine candidates for canine visceral leishmaniasis

“…In view of the fact that the current studies are testing recombinant antigens, this crucial pre-requisite in vaccine development was imperative to be investigated because an immune response to recombinant antigens not necessarily recognizes the corresponding native antigens. Moreover, since immunity to VL is primarily mediated by Th1 cells [17,35], the evaluation of the Th1/Th2 paradigm induced by a vaccine candidate is also a critical element to be investigated. The current studies were not aimed at investigating any protective effect of the two vaccine formulations because protection studies against VL in kenneled dogs have been a controversial issue mostly because the results obtained from this kind of experiment are not necessarily translated into the outcome of vaccine trials with unconfined dogs [15,28].…”

Immunoactivation and immunopathogeny during active visceral leishmaniasis

“…It has also been found to be important in susceptibility to visceral leishmaniasis 30,49 . It has been detected in different samples of human visceral leishmaniasis: as mRNA in bone marrow 36 , lymph node 27 , and spleen 38 aspirates and at high levels in serum 1,2,15,40,50,52,63,69 ; for further information see 51 .…”

“…The latter acts independently of IFN-g and is linked to the production of transforming growth factor beta (TGF-b). Susceptibility involves IL-10 (but not IL-4) and B cells 30 .…”