Enhanced resistance to acute infection with Trypanosoma cruzi in mice treated with an interferon inducer

James, Stephanie; Kipnis, Thereza Liberman; Sher, Alan; Hoff, Rodney

doi:10.1128/iai.35.2.588-593.1982

Cited by 35 publications

(8 citation statements)

References 23 publications

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“…(10,17), Trypanosoma cruzi (13), Toxoplasma gondii (19), and Babesia microti (10) showed alterations in NK anti-tumor cell activity in vitro; the nature of the alterations differed according to the parasite studied. Despite the observed association between parasite infection and NK functional alterations, no direct role for NK cells in host defenses against these infec- (13,18), altI active role for I significantly imp] but not bg/bg, mi( interferon induce (18).…”

Section: Discussionmentioning

confidence: 96%

Leishmaniasis in beige mice

Kirkpatrick¹,

Farrell²

1982

Infect Immun

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The courses of two protozoal diseases, cutaneous and visceral leishmaniasis, were examined in three groups of C57BL/6J mice. One group of mice was homozygous recessive for the beige gene (bg/bg). Beige mice are the genetic homologue of the human Chédiak-Higashi syndrome and, among other defects, are profoundly deficient in natural killer cell activity. Wild-type (+/+) mice, which respond to experimental cutaneous or visceral leishmaniasis by eventually eliminating their parasites, and heterozygous beige (bg/+) mice served as controls; both are phenotypically normal in natural killer cell activity, which is particularly high in the spleen. In bg/bg mice, the course of Leishmania tropica, a causative agent of cutaneous leishmaniasis, was similar to that in control mice after both primary and challenge inoculations. All groups of mice expressed similar humoral and cellular immune responses to L. tropica antigen. However, bg/bg mice failed to eliminate amastigotes of Leishmania donovani, a causative agent of visceral leishmaniasis, from their spleens over an observation period of 56 days, in contrast to bg/+ and +/+ controls. Similar levels of anti-leishmanial antibody were produced by all groups of mice, and all mice responded comparably to footpad injections of L. donovani antigen. The results of this study suggest a possible role for natural killer cells in recovery from L. donovani but not from L. tropica infection.

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Section: Discussionmentioning

confidence: 96%

Leishmaniasis in beige mice

Kirkpatrick¹,

Farrell²

1982

Infect Immun

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“…However, there are very few studies showing the effect of different tilorone analogues against microbial agents [14–17]. Thus, our aim was to detect a possible antimicrobial effect of tilorone analogues on several microorganisms, as well as their activity in the induction of resistance to fungal pathogens in an experimental systemic candidiasis in BALB/c mice.…”

Section: Discussionmentioning

confidence: 99%

Enhanced resistance to experimental systemic candidiasis in tilorone-treated mice

Ortega

Algarra

Serrano

et al. 2000

FEMS Immunology &Amp; Medical Microbiology

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Candida albicans is an increasingly important opportunistic fungal pathogen in immunocompromised patients. Natural killer (NK) cells constitute an important immune effector mechanism and are involved in the response to different pathological disorders. We wished to determine if this immune mechanism is involved in the specific response to C. albicans. Tilorone hydrochloride and related compounds have been described to display antiviral and antitumoral activity, as well as to enhance NK cell activity. In this study, we show the antimicrobial activity of different tilorone analogues and the enhanced resistance of tilorone-treated mice in experimental systemic candidiasis. We also present data suggesting that there is a correlation between NK cell activation and the resistance to experimental systemic candidiasis. Thus, it seems that the immunosurveillance of metastatic spread and the infection by C. albicans share some immune effector mechanisms, in particular activation of NK cells.

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“…In the early inflammatory response to such an infection, regulatory interactions mediated by cytokines could occur among these cell types. Thus, IFN-␥ has been shown to be an important mediator of resistance to T. cruzi (9,18,23,29). Whereas treatment with IFN-␥ is protective, the neutralization of endogenously produced IFN-␥ results in increased susceptibility during the acute stage of infection with T. cruzi.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-12 mediates resistance to Trypanosoma cruzi in mice and is produced by murine macrophages in response to live trypomastigotes

et al. 1996

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Host resistance to infection by Trypanosoma cruzi is dependent on both natural and acquired immune responses. During the first week of infection in mice, NK cell-derived gamma interferon (IFN-␥) is involved in controlling intracellular parasite replication, mainly through the induction of NO biosynthesis by activated macrophages. Interleukin-12 (IL-12) has been shown to be a powerful cytokine in inducing IFN-␥ synthesis by NK cells, as well as in mediating resistance to different intracellular protozoa. We have therefore studied the ability of T. cruzi to elicit IL-12 synthesis by macrophages and the role of this cytokine in controlling parasite replication during acute infection in mice. Our results show that macrophages cultured in the presence of live trypomastigote forms (but not epimastigotes) release IL-12 that can induce IFN-␥ production by normal spleen cells. IL-12 was detected in as little as 12 h after the addition of the trypomastigotes, and the level of IL-12 peaked at 48 h after the initial macrophage-parasite incubation. The addition of anti-IL-12 monoclonal antibody to macrophage-trypomastigote supernatants dose-dependently inhibited IFN-␥ production by naive splenocytes. Finally, the in vivo role of IL-12 in resistance to infection by T. cruzi was analyzed. Mice treated with anti-IL-12 monoclonal antibody had significantly increased parasitemia and mortality in comparison with those of control infected mice treated with control antibody. Together, these results suggest that macrophagederived IL-12 plays a major role in controlling the parasitemia in T. cruzi-infected mice and that the animal's resistance during the acute phase of infection may, at least in part, be a consequence of postinfection levels of IL-12.

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Enhanced resistance to acute infection with Trypanosoma cruzi in mice treated with an interferon inducer

Cited by 35 publications

References 23 publications

Leishmaniasis in beige mice

Leishmaniasis in beige mice

Enhanced resistance to experimental systemic candidiasis in tilorone-treated mice

Interleukin-12 mediates resistance to Trypanosoma cruzi in mice and is produced by murine macrophages in response to live trypomastigotes

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