First Author | Laskay T | Year | 1995 |
Journal | Eur J Immunol | Volume | 25 |
Issue | 8 | Pages | 2220-7 |
PubMed ID | 7664785 | Mgi Jnum | J:28176 |
Mgi Id | MGI:75802 | Doi | 10.1002/eji.1830250816 |
Citation | Laskay T, et al. (1995) Early parasite containment is decisive for resistance to Leishmania major infection. Eur J Immunol 25(8):2220-7 |
abstractText | We investigated the early spread of Leishmania major in various mouse strains. In BALB/c mice, which are extremely vulnerable to L. major infection, the parasites disseminated within 10-24 h from the site of subcutaneous footpad infection in to the popliteal lymph node, spleen, lung, liver and bone marrow. Application of recombinant (r)IL-12 prior to infection prevented the early dissemination of parasites into visceral organs and the animals healed the infection. In three mouse strains tested, C57BL/6, CBA/J and C3H/HeJ, which are all resistant to L. major infection, the parasites remained localized in the footpad and in the draining LN for 3 days without evidence of dissemination. In C57BL/6 mice, depletion of NK1.1+ cells or neutralization of interferon (IFN)-gamma prior to infection led to rapid parasite spreading with kinetics similar to those seen in susceptible animals. Depletion of either CD4+ or CD8+ T cells in vivo prior to infection did not alter the kinetics of dissemination in any mouse strain tested. Experiments with severe-combined immunodeficient mice provided further evidence that parasite containment depends on natural killer cells and IFN-gamma, but is independent of T cells. The finding that all resistant mouse strains restrict the spread of the parasites within the first 24 h after infection strongly suggests that early parasite containment is closely associated with a resistant phenotype. The data show that local restriction of parasites in the pre-T cell phase of the infection is mediated by the innate immune system and suggest that this function plays an important role in the development of a protective T cell response. |