Intracellular antimicrobial activity in the absence of interferon-γ: Effect of interleukin-12 in experimental visceral Leishmaniasis in interferon-γ gene-disrupted mice Academic Article Article uri icon

Overview

MeSH Major

  • Amphotericin B
  • Antiprotozoal Agents
  • Leishmaniasis, Visceral

abstract

  • Despite permitting uncontrolled intracellular visceral infection for 8 wk, interferon-gamma (IFN-gamma) gene knockout (GKO) mice infected with Leishmania donovani proceeded to reduce liver parasite burdens by 50% by week 12. This late-developing IFN-gamma-independent antileishmanial mechanism appeared to be dependent largely on endogenous tumor necrosis factor-alpha (TNF-alpha): L. donovani infection induced TNF-alpha mRNA expression in parasitized GKO livers and neutralization of TNF-alpha reversed control at week 12.7 d of treatment of infected GKO mice with interleukin-12 (IL-12) readily induced leishmanicidal activity and also partially restored the near-absent tissue granulomatous response, observations that for the first time expand the antimicrobial repertoire of IL-12 to include IFN-gamma-independent effects. The action of IL-12 against L. donovani was TNF-alpha dependent and required the activity of inducible nitric oxide synthase. These results point to the presence of an IFN-gamma-independent antimicrobial mechanism, mediated by TNF-alpha, which remains quiescent until activated late in the course of experimental visceral leishmaniasis. However, as judged by the effect of exogenous IL-12 this quiescent mechanism can readily be induced to rapidly yield enhanced intracellular antimicrobial activity.

publication date

  • April 7, 1997

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.1084/jem.185.7.1231

PubMed ID

  • 9104810

Additional Document Info

start page

  • 1231

end page

  • 9

volume

  • 185

number

  • 7