IL-4 reduces resistance of mice to Trypanosoma cruzi infection (original) (raw)
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Effects of Interleukin-4 Deprivation and Treatment on Resistance to Trypanosoma cruzi
Infection and Immunity, 2000
Trypanosoma cruzi (Y strain)-infected interleukin-4 −/− (IL-4 −/− ) mice of strains 129/J, BALB/c, and C57BL/6 showed no significant difference in parasitemia levels or end point mortality rates compared to wild-type (WT) mice. Higher production of gamma interferon (IFN-γ) by parasite antigen (Ag)-stimulated splenocytes was observed only for C57BL/6 IL-4 −/− mice. Treatment of 129/J WT mice with recombinant IL-4 (rIL-4), rIL-10, anti-IL-4, and/or anti-IL-10 monoclonal antibodies (MAbs) did not modify parasitism. However, WT mice treated with rIL-4 and rIL-10 had markedly increased parasitism and suppressed IFN-γ synthesis by spleen cells stimulated with parasite Ag, concanavalin A, or anti-CD3. Addition of anti-IL-4 MAbs to splenocyte cultures from infected WT 129/J, BALB/c, or C57BL/6 mice failed to modify IFN-γ synthesis levels; in contrast, IL-10 neutralization increased IFN-γ production and addition of rIL-4 and/or rIL-10 diminished IFN-γ synthesis. We conclude that endogenous I...
International Journal for Parasitology, 2007
Innate and adaptive immunity collaborate in the protection of intracellular pathogens including Trypanosoma cruzi infection. However, the parasite molecules that regulate the host immune response have not been fully identified. We previously demonstrated that the immunisation of C57BL/6 mice with cruzipain, an immunogenic T. cruzi glycoprotein, induced a strong specific T-cell response. In this study, we demonstrated that active immunisation with cruzipain was able to stimulate nitric oxide (NO) production by splenocytes. Immune cells also showed increased inducible nitric oxide synthase protein and mRNA expression. Spleen adherent cells secreted high levels of IFN-c and IL-12. Microbicidal activity in vitro was mainly mediated by reactive nitrogen intermediaries and IFN-c, as demonstrated by the inhibitory effects of NO synthase inhibitor or by IFN-c neutralisation. Specific T-cells were essential for NO, IFN-c and TNF-a production. Furthermore, we reported that cruzipain enhanced CD80 and major histocompatibility complex-II molecule surface expression on F4/80+ spleen cells. Interestingly, we also showed that cruzipain up-regulated toll like receptor-2 expression, not only in F4/80+ but also in total spleen cells which may be involved in the effector immune response. Our findings suggest that a single parasite antigen such as cruzipain, through adaptive immune cells and cytokines, can modulate the macrophage response not only as antigen presenting cells, but also as effector cells displaying enhanced microbicidal activity with reactive nitrogen intermediary participation. This may represent a mechanism that contributes to the immunoregulatory process during Chagas disease. Ó
Detrimental effect of nitric oxide on Trypanosoma cruzi and Leishmania major like cells
Acta Tropica, 1997
The production of nitric oxide (NO) by activated macrophages has been reported to be a non-specific immune-effect mechanism against several parasites. In this work we investigate whether the NO has a detrimental effect on the intracellular parasites of the genus Leishmania and as well as Trypanosoma cruzi. This was assessed by co-cultivating infective Leishmania promastigotes and T. cruzi trypomastigotes and non-infective T. cruzi epimastigotes forms of the parasites in the presence of the NO releasing molecule, S-nitroso-N-acetyl-DL-penicillamine (SNAP). We demonstrate that the NO has the ability to inhibits the growth of all parasites in a concentration dependent manner. In addition, by analysing purified protein and cell homogenates of L. major (promastigotes) and T. cruzi (epimastigotes and trypomastigotes) we demonstrated that the NO may regulate the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity of both parasites. © 1997 Elsevier Science B.V.
Immunology, 2003
Interleukin-12 (IL-12) is essential to resistance to Trypanosoma cruzi infection because it stimulates the synthesis of interferon-g (IFN-g) that activates macrophages to a parasiticidal effect. Investigation of mice deprived of IL-12 genes (IL-12 knockout mice) has confirmed the important role of IL-12 and IFN-g in controlling parasitism in T. cruzi infection. However, it has not yet been addressed whether a shift towards a T helper type 2 (Th2) pattern of cytokine response occurred in these mice that might have contributed to the aggravation of the infection caused by IL-12 deprivation. We examined the course of T. cruzi (Y strain) infection and the regulation of cytokine responses and nitric oxide production in C57BL/6 IL-12 p40-knockout mice. The mutant mice were extremely susceptible to the infection as evidenced by increased parasitaemia, tissue parasitism and mortality in comparison with the control C57BL/6 mouse strain (wild-type) that is resistant to T. cruzi. A severe depletion of parasite-antigen-specific IFN-g response, without an increase in IL-4 or IL-10 production, accompanied by reduced levels of nitric oxide production was observed in IL-12 knockout mice. We found no evidence of a shift towards a Th2-type cytokine response. In IL-12 knockout mice, the residual IFN-g production is down-regulated by IL-10 but not by IL-4 and nitric oxide production is stimulated by tumour necrosis factor-a. Parasite-specific immunoglobulin G1 antibody levels were similar in IL-12 knockout and wild-type mice, whereas IL-12 knockout mice had much higher levels of immunoglobulin G2b.
Trypanosoma cruzi:IL-10, TNF, IFN-γ, and IL-12 Regulate Innate and Acquired Immunity to Infection
Experimental Parasitology, 1996
Control of the acute phase of Trypanosoma cruzi infections is critically dependent on cytokinemediated macrophage activation to intracellular killing. We investigated the roles of IL-10, TNF, IFN-␥, and IL-12 in the control of parasitism by innate and specific immunity. Mice with disrupted IL-10 genes (IL-10 KO) infected with Y strain T. cruzi have lower parasite numbers in the blood and tissues and higher IFN-␥ and nitric oxide (NO) production by spleen cells than wild type (WT) mice. Treatment of IL-10 KO and WT mice with recombinant IL-10 resulted in increased parasitemia. Mice with disrupted recombinase-activating genes (RAG/KO) that lack B and T cells provided a model for determining the importance of innate immunity to resistance. RAG/KO and WT mice had similar parasitemia levels until Day 13 of infection, suggestive of effective control of parasitism by the innate immune system during the early phase of infection; from then on parasitemia was higher in RAG/KO. Double RAG/IL-10 KO mice and RAG/KO mice had superimposable parasitemia curves, indicating that in the absence of T and B cells, endogenous IL-10 does not limit the efficacy of the innate immune system. Treatment of infected RAG/KO, IL-10/KO, and WT mice with anti-IFN-␥, anti-TNF, or anti-IL-12 neutralizing mAbs increased parasitemia levels showing the importance of endogenous production of these cytokines in the control of parasitism by innate and specific immune responses. Spleen cells from anti-IL12-treated WT mice had diminished production of IFN-␥ and NO, suggesting that early IFN-␥ synthesis is most dependent on IL-12 stimulation.
OnLine Journal of Biological Sciences, 2015
The study of biotherapies as an intervention in experimental models of infection is a possible means to understand the effects of these highly diluted medications. The present study evaluated the immunological and parasitological effects of biotherapies that were prepared from mouse serum that was uninfected (sarcode: BSNI 13cH group) and chronically infected with the Y strain of T. cruzi (nosode: BSI 13cH group), dynamization 13cH, in male Swiss mice at 28 days of age. On days 0 and 12 after infection (a.i.), the BSNI 13cH group exhibited a pronounced Th1 response that was attributable to a reduction of interleukin-4 (IL-4) concentrations, with no significant differences in interferon-γ (IFN-γ) concentrations and a decrease in IL-17A concentrations on day 0 a.i. compared with the control and BSI 13cH groups. However, this cytokine balance was not sufficient to alter blood parasitemia in treated animals, likely because of a decrease in IFN-γ concentrations on day 8 a.i., thus hindering a more effective Th1 response. In contrast, the BSI 13cH group presented a pronounced Th2 response that was attributable to an increase in IL-4 concentrations (on days 0 and 8 a.i.) and a decrease in IFN-γ concentration (on day 12 a.i.) compared with the control and BSNI 13cH groups. This cytokine balance suppressed the immune response to T. cruzi in murine infection, resulting in a significant increase in blood parasitemia, decrease in the patent period and subsequently a decrease in survival time. The results indicate that these highly diluted medications differentially modulate the immune system and represent a substantial contribution to the field of homeopathic medicine, providing evidence of the action of these medications.
OnLine Journal of Biological Sciences, 2015
The study of biotherapies as an intervention in experimental models of infection is a possible means to understand the effects of these highly diluted medications. The present study evaluated the immunological and parasitological effects of biotherapies that were prepared from mouse serum that was uninfected (sarcode: BSNI 13cH group) and chronically infected with the Y strain of T. cruzi (nosode: BSI 13cH group), dynamization 13cH, in male Swiss mice at 28 days of age. On days 0 and 12 after infection (a.i.), the BSNI 13cH group exhibited a pronounced Th1 response that was attributable to a reduction of interleukin-4 (IL-4) concentrations, with no significant differences in interferon-γ (IFN-γ) concentrations and a decrease in IL-17A concentrations on day 0 a.i. compared with the control and BSI 13cH groups. However, this cytokine balance was not sufficient to alter blood parasitemia in treated animals, likely because of a decrease in IFN-γ concentrations on day 8 a.i., thus hindering a more effective Th1 response. In contrast, the BSI 13cH group presented a pronounced Th2 response that was attributable to an increase in IL-4 concentrations (on days 0 and 8 a.i.) and a decrease in IFN-γ concentration (on day 12 a.i.) compared with the control and BSNI 13cH groups. This cytokine balance suppressed the immune response to T. cruzi in murine infection, resulting in a significant increase in blood parasitemia, decrease in the patent period and subsequently a decrease in survival time. The results indicate that these highly diluted medications differentially modulate the immune system and represent a substantial contribution to the field of homeopathic medicine, providing evidence of the action of these medications.