concanavalin-a and Leishmaniasis--Cutaneous

Cutaneous leishmaniasis triggers a varied immune response depending on parasite and host factors, which in turn can be influenced by nutrients. The resistance to the infection is associated with the Th1 type of cytokine production. The Th1 type can be reduced as a consequence of zinc deficiency, which may increase the risk for chronicity of the infection. Using in vitro and ex vivo models, we studied the influence of zinc supplementation on the immune response in patients with cutaneous leishmaniasis treated with antimony and the data were also compared to those of matched controls. Twenty-nine patients with cutaneous leishmaniasis (n=14 in zinc-supplemented group [45mg/day] and n=15 in placebo group) were treated by intramuscular injections of antimony for 20 days and took supplements for 60 days. Immunoglobulins in plasma and cell proliferation, IFN-γ production and CD markers of isolated peripheral blood mononuclear cells (PBMC) were measured. It was found that the cellular immune response of the patients maintained its activity as assessed by the ability of the PBMC to proliferate and produce IFN-γ in response to concanavalin A. Moreover, there was no difference in these variables between the zinc-supplemented and placebo groups after 60 days. The addition of zinc sulphate in vitro to PBMC reduced the IFN-γ production in the placebo group only. It is concluded that the cellular immune response of the cutaneous leishmaniasis patients remained active during treatment by antimony when compared to that of controls. It was not possible to document an additional effect of zinc supplementation for 60 days on the immune response.

Topics: Case-Control Studies; Cell Proliferation; Concanavalin A; Dietary Supplements; Humans; Immunity; Immunoglobulins; Interferon-gamma; Leishmaniasis, Cutaneous; Leukocytes, Mononuclear; Lymphocyte Count; Zinc

In this study, we have the objective of evaluating the lymphoproliferative response and determining interferon (IFN)-gamma and interleukin (IL)-10 cytokine production in the peripheral blood mononuclear cells (PBMC) of patients with American tegumentary leishmaniasis prior and post 12 months of chemotherapy treatment with meglumine antimoniate compared with the PBMC of noninfected donors. Lymphoproliferation, such as cytokine production, was evaluated through in vitro stimulus with the soluble antigenic fraction from Leishmania (Viannia) braziliensis promastigotes (1.25 microg/ml) and Concanavalin A (2.5 microg/ml). Patients showed a significant lymphoproliferative response prior and post treatment compared with the control group. Similar result, prior to chemotherapy treatment, was observed in IFN-gamma and IL-10 production when patients were compared with the control group. After chemotherapy treatment, PBMC lymphoproliferative response of the patients revealed an increase, whereas patients have shown a decrease in IFN-gamma levels and an increase in IL-10, although without statistical difference. These results may indicate that the patients produced a specific cellular response to the soluble antigenic fraction suggesting that besides Th1 and Th2 dichotomy, immunological regulation mechanisms with the participation of memory T cells and regulatory T cells could be present in the clinical evolution of these patients. This understanding will allow the study and identification of new L. (V.) braziliensis molecules potentially candidates to vaccines.

Topics: Animals; Antigens, Protozoan; Case-Control Studies; Concanavalin A; Female; Follow-Up Studies; Humans; Immunity, Cellular; Interferon-gamma; Interleukin-10; Leishmania braziliensis; Leishmaniasis, Cutaneous; Leukocytes, Mononuclear; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Statistics, Nonparametric; Treatment Outcome

Leishmania mexicana mutants lacking cysteine proteinase genes cpa (delta cpa), cpb (delta cpb), or both cpa and cpb (delta cpa/cpb) have been generated by targeted gene disruption. Delta cpa mutants produce a disease phenotype in BALB/c mice close to that of wild-type L. mexicana, but delta cpb mutants are much less infective, producing very slowly growing small lesions, and delta cpa/cpb double mutants do not induce lesion growth. Immunologic analysis of Ab isotype during infection and splenocyte IFN-gamma, IL-2, and IL-4 production following stimulation with Leishmania Ag or Con A indicates that there was a significant shift from a predominantly Th2-associated immune response in mice infected with wild-type L. mexicana to a Th1-associated response in mice inoculated with delta cpb or delta cpa/cpb. Significantly, delta cpa altered the balance of the immunologic response to a lesser extent than did the other mutants. Similar disease outcomes and switches in the Th1/Th2 balance were also observed when other L. mexicana-susceptible mouse strains were infected with the mutants. BALB/c and C57BL/6 mice vaccinated with delta cpa/cpb and CBA/Ca mice vaccinated with delta cpb or delta cpa/cpb were subsequently more resistant, to varying degrees, than were untreated mice to infection with wild-type parasites, as measured by development of lesions and parasite burden. These data implicate leishmanial cysteine proteinases not only as parasite virulence factors but also in modulation of the immune response and provide strong encouragement that cysteine proteinase-deficient L. mexicana mutants are candidate attenuated live vaccines.

Topics: Animals; Concanavalin A; Cysteine Endopeptidases; Gene Deletion; Immunization; Interferon-gamma; Interleukin-2; Interleukin-4; Leishmania mexicana; Leishmaniasis, Cutaneous; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred CBA; Protozoan Proteins; Protozoan Vaccines; Th1 Cells; Th2 Cells; Vaccines, Attenuated; Virulence