Journal article
Local suppression of IFN-gamma in hepatic granulomas correlates with tissue-specific replication of Leishmania chagasi
The Journal of immunology (1950), Vol.156(6), pp.2231-2239
03/15/1996
DOI: 10.4049/jimmunol.156.6.2231
PMID: 8690913
Abstract
BALB/c mice are susceptible to infection with the visceralizing species of Leishmania, Leishmania chagasi. The parasite load initially rises in the liver and spontaneously subsides, whereas parasite multiplication begins later and remains lower in the spleen. To investigate whether this organ-specific multiplication of L. chagasi correlates with localized immune responses, we compared cytokine production by splenic vs hepatic immune cells. Livers from infected mice contained granulomas harboring intracellular L. chagasi amastigotes, whereas few amastigotes were present in the spleen. FACS analysis granuloma cells showed granuloma lymphocytes expressed a memory/effector phenotype. Granuloma cells cultured in vitro produced IL-10 and IL-6 but no detectable IFN-gamma, IL-4 or IL-5. In contrast, splenocytes from the same animals secreted IFN-gamma, IL-4, IL-6, and IL-10. T cells were depleted from granuloma cells by immune lysis, and the results indicated that IL-10 and IL-6 were derived at least in part from a non-T cell compartment. Paradoxically, FACS-purified Thy-1+ granuloma lymphocytes were able to produce IFN-gamma in the absence of other granuloma cells, suggesting IFN-gamma production might usually be inhibited by a granuloma-associated non-T cell element. Coculture of splenocytes with either granuloma cells or supernatants from granuloma cultures inhibited the usual splenocyte production of IFN-gamma and IL-4 but not IL-10. Thus, there may be a unique granuloma-associated suppressive factor accounting for the absence of IFN-gamma in hepatic granuloma cultures. It may be the absence of IFN-gamma in the liver and presence in the spleen that allows or inhibits parasite survival, respectively, in these different locations.
Details
- Title: Subtitle
- Local suppression of IFN-gamma in hepatic granulomas correlates with tissue-specific replication of Leishmania chagasi
- Creators
- Mary E Wilson - Department of Internal Medicine, University of Iowa, Iowa City 52242, USAMatyas SandorArthur M BlumBetty M YoungAhmed MetwaliDavid ElliottRichard G LynchJoel V Weinstock
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.156(6), pp.2231-2239
- Publisher
- United States
- DOI
- 10.4049/jimmunol.156.6.2231
- PMID
- 8690913
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Grant note
- AM38327 / NIADDK NIH HHS AI30126 / NIAID NIH HHS AI32135 / NIAID NIH HHS
- Language
- English
- Date published
- 03/15/1996
- Academic Unit
- Microbiology and Immunology; International Programs; Epidemiology; Internal Medicine
- Record Identifier
- 9984001125302771
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