A natural model of Leishmania major infection reveals a prolonged "silent"phase of parasite amplification in the skin before the onset of lesion formation and immunity

Citation
Y. Belkaid et al., A natural model of Leishmania major infection reveals a prolonged "silent"phase of parasite amplification in the skin before the onset of lesion formation and immunity, J IMMUNOL, 165(2), 2000, pp. 969-977
Citations number
57
Categorie Soggetti
Immunology
Journal title
JOURNAL OF IMMUNOLOGY
ISSN journal
00221767 → ACNP
Volume
165
Issue
2
Year of publication
2000
Pages
969 - 977
Database
ISI
SICI code
0022-1767(20000715)165:2<969:ANMOLM>2.0.ZU;2-0
Abstract
A model of Leishmania major infection in C57BL/6 mice has been established that combines two main features of natural transmission: low dose (100 meta cyclic promastigotes) and inoculation into a dermal site (the ear dermis), The evolution of the dermal lesion could be dissociated into two distinct p hases, The initial "silent" phase, lasting 4-5 wk, favored establishment of the peak load of parasites in the dermis in the absence of lesion formatio n or any overt histopathologic changes in the site. The second phase corres ponds to the development of a lesion associated with an acute infiltration of neutrophils, macrophages, and eosinophils into the dermis and was coinci dent with the killing of parasites in the site. The onset of immunity/patho logy was correlated with the appearance of cells staining for IL-12p40 and IFN-gamma in the epidermal compartment, and an expansion of T cells capable of producing IFN-gamma in the draining lymph node. Parasite growth was not enhanced over the first 4.5 wk in anti-CD4-treated mice, SCID mice, or C57 BL/6 mice deficient in IL-12p40, IFN-gamma, CD40 ligand, or inducible NO sy nthase, These mice all failed to ultimately control infection in the site, but in some cases (anti-CD4 treated, IL-12p40(-/-), CD40 ligand(-/-), and S CID) high dermal parasite loads were associated with little or no pathology . These results extend to a natural infection model a role for Th1 cells in both acquired resistance and lesion formation, and document the remarkable avoidance of this response during a prolonged phase of parasite amplificat ion in the skin .