Granzyme-mediated regulation of host defense in the liver in experimental Leishmania donovani infection. Academic Article uri icon

Overview

abstract

  • In the livers of susceptible C57BL/6 (B6) mice infected with Leishmania donovani, CD8(+) T cell mechanisms are required for granuloma assembly, macrophage activation, intracellular parasite killing, and self-cure. Since gene expression of perforin and granzymes A and B (GzmA and GzmB), cytolytic proteins linked to CD8(+) cell effector function, was enhanced in infected liver tissue, B6 mice deficient in these granular proteins were used to gauge host defense roles. Neither perforin nor GzmA was required; however, mice deficient in GzmB (GzmB(-/-), GzmB cluster(-/-), and GzmA×B cluster double knockout [DKO] mice) showed both delayed granuloma assembly and initially impaired control of parasite replication. Since these two defects in B6 mice were limited to early-stage infection, innately resistant 129/Sv mice were also tested. In this genetic setting, expression of both innate and subsequent T (Th1) cell-dependent acquired resistance, including the self-cure phenotype, was entirely derailed in GzmA×B cluster DKO mice. These results, in susceptible B6 mice for GzmB and in resistant 129/Sv mice for GzmA and/or the GzmB cluster, point to granzyme-mediated host defense regulation in the liver in experimental visceral leishmaniasis.

publication date

  • December 1, 2014

Research

keywords

  • Granzymes
  • Leishmania donovani
  • Leishmaniasis, Visceral
  • Liver
  • Macrophages
  • T-Lymphocytes, Cytotoxic

Identity

PubMed Central ID

  • PMC4294235

Scopus Document Identifier

  • 84921341764

Digital Object Identifier (DOI)

  • 10.1128/IAI.02418-14

PubMed ID

  • 25452549

Additional Document Info

volume

  • 83

issue

  • 2