Effect of anti-γ-interferon and anti-interleukin-4 administration on the resistance of mice against infection with reticulotropic and myotropic strains of Trypanosoma cruzi

Petray, Patricia; Rottenberg, Martı́n E.; Bertot, Gustavo M.; Corral, Ricardo S.; Díaz, Alcira Ofélia; Örn, Anders; Grinstein, S

doi:10.1016/0165-2478(93)90151-q

Cited by 49 publications

(46 citation statements)

References 19 publications

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“…Trypanosoma cruzi is a potent inducer of IFN-g production in vivo IFN-g is known to play a central role in the control of infection with T. cruzi [7][8][9][10]. In accordance with previous reports using other T. cruzi strains, we found using the Tehuantepec and Tulahuén strains that IFN-g is the predominant cytokine produced after infection of BALB/c mice.…”

Section: Expression Of T Cruzi-specific Mrna In the Spleen After Infsupporting

confidence: 79%

“…IFN-g plays a critical role in resistance to infection with T. cruzi [7][8][9][10]. Here, we have investigated the distribution and kinetics of the gene expression of IFN-g and of two cytokines that stimulate its production.…”

Section: Discussionmentioning

confidence: 99%

“…Endogenous IFN-g seems to play a central role in the control of infection [7,8]. Passive administration of IFN-g results in an increased clearance of the parasite and a reduced mortality of infected mice [9], while anti-IFN-g MoAbs augment the susceptibility to acute T. cruzi infection [10]. Furthermore, BALB.Xid mice that produce higher levels of IFN-g than susceptible normal BALB/c mice are relatively resistant to infection [11].…”

Section: Introductionmentioning

confidence: 99%

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Trypanosoma cruzi induces strong IL-12 and IL-18 gene expression in vivo: correlation with interferon-gamma (IFN-γ) production

Büschenfelde

Cramer

Trumpfheller

et al. 1997

Clinical and Experimental Immunology

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SUMMARYIFN-g, produced after infection with Trypanosoma cruzi, has been shown to be crucial in the determination of resistance or susceptibility. We have performed a detailed study on the expression of IFN-g and of the IFN-g-inducing cytokines IL-12 and IFN-g-inducing factor (IGIF)/IL-18 with regard to time course and tissue localization. IFN-g was present in high amounts in the serum and in the supernatants of unseparated spleen cells and isolated CD4þ and CD8 þ T cells from the spleens of infected mice which were stimulated ex vivo with T. cruzi. Using the in situ hybridization technique we demonstrate that IL-12 p40 messages were expressed in the spleen and increased during infection, correlating with the expression of IFN-g transcripts. Furthermore, we show for the first time that the mRNA for the cytokine IL-18 was induced by a parasitic infection and that this expression increased during infection with T. cruzi. Interestingly, the message for IL-18 was produced earlier during infection and already had declined until day 38, when IFN-g and IL-12 p40 transcripts were optimally expressed. Surprisingly, the changes in IL-12 and IL-18 mRNA production were clearly seen only by in situ hybridization, but less clearly by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). This is possibly due to the extensive activation and proliferation of spleen cells observed during infection leading to a dilution of these specific mRNAs.

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Section: Expression Of T Cruzi-specific Mrna In the Spleen After Infsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Trypanosoma cruzi induces strong IL-12 and IL-18 gene expression in vivo: correlation with interferon-gamma (IFN-γ) production

Büschenfelde

Cramer

Trumpfheller

et al. 1997

Clinical and Experimental Immunology

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“…In contrast, a linkage between Th1 responses and resistance has not been so firmly established with respect to T. cruzi infection. The results of some studies suggest a requirement for a balanced type 1 and type 2 response to control infection with T. cruzi (23,26,47), while other studies attribute protection to the production of type 1 but not type 2 cytokines in vivo in different mouse and parasite strain combinations (18 -20, 24, 48, 49).…”

Section: Discussionmentioning

confidence: 97%

“…Similar to infections with other intracellular pathogens (Leishmania (13), Mycobacterium (14), and Listeria (15)), where a strong Th1 response protects whereas a Th2 response increases susceptibility to infection (16,17), there is some evidence for a protective role of Th1 cells (18) and an exacerbative role for Th2 cells (19) in T. cruzi infection. Production of the type 1 cytokine, IFN-␥, in the acute phase of T. cruzi infection is associated with resistance (20 -22) and depletion of IFN-␥ exacerbates parasitemia and results in increased mortality in T. cruzi-infected mice (23,24). Similarly, IL-12, an inducer of the type 1 cytokine response, promotes resistance to T. cruzi in murine models (25).…”

mentioning

confidence: 99%

Antigen-Specific Th1 But Not Th2 Cells Provide Protection from Lethal Trypanosoma cruzi Infection in Mice

Kumar

Tarleton

2001

The Journal of Immunology

106

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Infection with Trypanosoma cruzi results in the development of both type 1 and type 2 patterns of cytokine responses during acute and chronic stages of infection. To investigate the role of Th1 and Th2 subsets of CD4+ T cells in determining the outcome of T. cruzi infection in mice, we have developed T. cruzi clones that express OVA and have used OVA-specific TCR-transgenic T cells to generate OVA-specific Th1 and Th2 cells. BALB/c mice receiving 107 OVA-specific Th1 cells and then challenged with OVA-expressing T. cruzi G-OVA.GPI showed significantly lower parasitemia and increased survival in comparison to mice that received no cells. In contrast, recipients of OVA-specific Th2 cells developed higher parasitemias, exhibited higher tissue parasitism and inflammation, and had higher mortality than recipients of Th1 cells after infection with T. cruzi G-OVA.GPI. Mice receiving a mixture of both Th1 and Th2 OVA-specific cells also were not protected from lethal challenge. The protective effect of the OVA-specific Th1 cells was OVA dependent as shown by the fact that transfer of OVA-specific Th1 or Th2 cells failed to alter the course of infection or disease in mice challenged with wild-type T. cruzi. Immunohistochemical analysis of OVA-specific Th1 and Th2 cells at 4, 15, and 30 days postinfection revealed the persistence and expansion of these cells in mice challenged with T. cruzi G-OVA.GPI but not in mice infected with wild-type T. cruzi. We conclude that transfer of Ag-specific Th1 cells but not Th2 cells protect mice from a lethal infection with T. cruzi.

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Increased susceptibility of Fas ligand-deficientgld mice toTrypanosoma cruzi infection due to a Th2-biased host immune response

et al. 1999

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Infection of BALB/c mice with Trypanosoma cruzi resulted in up-regulated expression of Fas and Fas ligand (FasL) mRNA by splenic CD4 + T cells, activation-induced CD4 + T cell death (AICD), and in Fas : FasL-mediated cytotoxicity. When CD4 + T cells from infected mice were co-cultured with T. cruzi-infected macrophages, onset of AICD exacerbated parasite replica-tion. CD4 + T cells from T. cruzi-infected FasL-deficient BALB gld/gld mice had no detectable AICD in vitro and their activation with anti-TCR did not exacerbate T. cruzi replication in mac-rophages. However, infection of BALB gld/gld mice with T. cruzi resulted in higher and more prolonged parasitemia, compared to wild-type mice. Secretion of Th2 cytokines IL-10 and IL-4 by CD4 + T cells from infected gld mice was markedly increased, compared to controls. In addition, in vivo injection of anti-IL-4 mAb, but not of an isotype control mAb, reduced parasitemia in both gld and wild-type mice. These results indicate that, besides controlling CD4 + T cell AICD and parasite replication in vitro, an intact Fas : FasL pathway also controls the host cytokine response to T. cruzi infection in vivo, being required to prevent an exacerbated Th2-type immune response to the parasite.

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Effect of anti-γ-interferon and anti-interleukin-4 administration on the resistance of mice against infection with reticulotropic and myotropic strains of Trypanosoma cruzi

Cited by 49 publications

References 19 publications

Trypanosoma cruzi induces strong IL-12 and IL-18 gene expression in vivo: correlation with interferon-gamma (IFN-γ) production

Trypanosoma cruzi induces strong IL-12 and IL-18 gene expression in vivo: correlation with interferon-gamma (IFN-γ) production

Antigen-Specific Th1 But Not Th2 Cells Provide Protection from Lethal Trypanosoma cruzi Infection in Mice

Increased susceptibility of Fas ligand-deficientgld mice toTrypanosoma cruzi infection due to a Th2-biased host immune response

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