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Leishmania major: differential resistance to infection in C57BL/6 (high interferon-alpha/beta) and congenic B6.C-H-28c (low interferon-alpha/beta) mice.
- Source :
-
Experimental parasitology [Exp Parasitol] 1996 Nov; Vol. 84 (2), pp. 136-43. - Publication Year :
- 1996
-
Abstract
- In murine cutaneous leishmaniasis caused by Leishmania major (Lm), resistance often associates with the outgrowth of Lm-specific Th1 cells. Parasites are eliminated by Th1-mediated activation of infected macrophages (M phi) which destroy Lm by producing toxic nitrogen and oxygen radicals. The cytokine IFN-alpha activates microbicidal functions of M phis and facilitates outgrowth of Th1 cells. Therefore, we compared the course of infection with Lm in resistant C57BL/6 mice, bearing the If-1h high expression allele for IFN-alpha/beta, with the congenic B6.C-H-28c mouse, bearing the If-1I low expression allele from the Lm-susceptible BALB/c strain. We observed that B6.C-H-28c animals developed up to 70% larger footpad lesions and harbored up to 1000-fold more parasites than C57BL/6 mice. Furthermore, peak Lm-specific IFN-gamma production in the B6.C-H-28c animals was lower and delayed by approximately 2 weeks, whereas IL-4 production was higher and persisted approximately 2 weeks longer. Since these results suggested that IFN-alpha/beta plays a protective role in mice infected with Lm, we determined whether infusing B6.C-H-28c mice with IFN-alpha would influence the course of infection with Lm. Unfortunately, the mice developed severe peritoneal hemorrhaging in response to injection with IFN-alpha. Therefore, we examined the ability of IFN-alpha to activate M phis to destroy Lm in vitro. We observed that rIFN-alpha could synergize with subactivating doses of LPS to activate both C57BL/6 and BALB/c peritoneal M phis to produce NO and to kill intracellular Lm. Taken as a whole, these results suggest that type I interferons may play a protective role in cutaneous leishmaniasis.
- Subjects :
- Animals
Disease Susceptibility
Immunity, Innate
Interferon Type I administration & dosage
Interferon Type I pharmacology
Interferon-alpha biosynthesis
Interferon-alpha genetics
Interferon-beta biosynthesis
Interferon-beta genetics
Lipopolysaccharides pharmacology
Macrophage Activation
Macrophages, Peritoneal immunology
Macrophages, Peritoneal metabolism
Macrophages, Peritoneal parasitology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Nitric Oxide biosynthesis
Recombinant Proteins
Th1 Cells immunology
Interferon-alpha immunology
Interferon-beta immunology
Leishmania major immunology
Leishmaniasis, Cutaneous immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0014-4894
- Volume :
- 84
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Experimental parasitology
- Publication Type :
- Academic Journal
- Accession number :
- 8932763
- Full Text :
- https://doi.org/10.1006/expr.1996.0099