Multiple host defense defects in failure of C57BL/6 ep/ep (pale ear) mice to resolve visceral Leishmania donovani infection
| Autor: | June Hariprashad, Mark Y. Stoeckle, D F McDermott, Henry W. Murray |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Antimony
T-Lymphocytes Immunology Leishmania donovani Antiprotozoal Agents Spleen Microbiology Interferon-gamma Mice Immune system Th2 Cells Amphotericin B medicine Macrophage Animals Interferon gamma Interleukin 4 biology Lymphokine biology.organism_classification Molecular biology Immunity Innate Mice Mutant Strains Causality Mice Inbred C57BL Infectious Diseases medicine.anatomical_structure Liver Cytokines Leishmaniasis Visceral Parasitology Tumor necrosis factor alpha Interleukin-4 medicine.drug Research Article |
| Zdroj: | Infection and immunity. 64(1) |
| ISSN: | 0019-9567 |
| Popis: | Euthymic C57BL/L ep/ep (pale ear [PE]) mice halt the visceral replication of intracellular Leishmania donovani but fail to properly resolve infection. A previous study identified an isolated defect in tissue granuloma formation in these mice; CD4+ and CD8+ cell number, gamma interferon (IFN-gamma) production, and macrophage antimicrobial activity in vitro were all intact. New in vivo results reported here suggest a considerably more complex immune defect, with evidence indicating (i) enhanced control over L. donovani after transfer of normal C57BL/6 spleen cells, (ii) a partially suppressive Th2 cell-associated response mediated by interleukin-4 (IL-4) but not reversed by CD4+ cell depletion, (iii) absent responses to endogenous Th1 cell lymphokines (IFN-gamma and IL-2) but preserved responsiveness to endogenous tumor necrosis factor alpha, (iv) absent responses to exogenous treatment with recognized antileishmanial cytokines (IFN-gamma, IL-2, IL-12, and granulocyte-macrophage colony-stimulating factor [GM-CSF]) not corrected by transfer of C57BL/6 spleen cells, and (v) a deficient response to antimony chemotherapy. Defective hepatic granuloma formation was not corrected by transfer of C57BL/6 spleen cells or by anti-IL-4 administration. While treatment with IL-2 and GM-CSF modified the tissue reaction and induced selected effector cells to encase tissue macrophages, no antileishmanial activity resulted. Together, these observations suggest that the failure of PE mice to resolve visceral L. donovani infection likely represents expression of multiple suboptimal immune responses and/or partial defects, probably involving a combination of T-cell dysfunction, a Th2 cell response, and target cell (macrophage) hyporesponsiveness. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|