Preformed membrane-associated stores of interleukin (IL)-12 are a previously unrecognized source of bioactive IL-12 that is mobilized within minutes of contact with an intracellular parasite

Marlon Quinones, Sunil K. Ahuja, Peter C. Melby, Lyle Pate, Robert L. Reddick, Seema S. Ahuja

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

The prevailing paradigm is that production of the interleukin (IL)-12 p70 heterodimer, a critical T helper cell type 1 (Th1)-inducing cytokine, depends on the induced transcription of the p40 subunit. Concordant with this paradigm, we found that dendritic cells (DCs) produced IL-12 p70 only after at least 2-4 h of stimulation with lipopolysaccharide plus interferon γ. However, using several complementary experimental approaches, including electron and confocal microscopy, we now show that resting murine and human myeloid cells, including macrophages/DCs and DC-rich tissues, contain a novel source of bioactive IL-12 that is preformed and membrane associated. These preformed, membrane-associated IL-12 p70 stores are released within minutes after in vitro or in vivo contact with Leishmania donovani, an intracellular pathogen. Our findings highlight a novel source of bioactive IL-12 that is readily available for the rapid initiation of Th1 host responses to pathogens such as Leishmania species.

Original languageEnglish (US)
Pages (from-to)507-515
Number of pages9
JournalJournal of Experimental Medicine
Volume192
Issue number4
DOIs
StatePublished - Aug 21 2000
Externally publishedYes

Keywords

  • Dendritic cells
  • IL-12 p70
  • Leishmania
  • Membrane
  • Th1/Th2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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