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

doi:10.1084/jem.192.4.507

Published online 14 August 2000.

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© The Rockefeller University Press, 0022-1007/2000/8/507/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 4, August 21, 2000 507-516

Original Article

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^a,b, Sunil K. Ahuja^a,b, Peter C. Melby^a,b, Lyle Pate^b, Robert L. Reddick^c, and Seema S. Ahuja^a,b
^a South Texas Veterans Health Care System, Audie L. Murphy Division, the
^b Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900
^c Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900

Correspondence to: Seema S. Ahuja, Department of Medicine (MC 7870), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900. Tel:210-567-4691 Fax:210-567-4654 E-mail:ahuja{at}uthscsa.edu.

The prevailing paradigm is that production of the interleukin(IL)-12 p70 heterodimer, a critical T helper cell type 1 (Th1)–inducingcytokine, 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 ofstimulation with lipopolysaccharide plus interferon ${gamma}$ . However,using several complementary experimental approaches, includingelectron and confocal microscopy, we now show that resting murineand human myeloid cells, including macrophages/DCs and DC-richtissues, contain a novel source of bioactive IL-12 that is preformedand membrane associated. These preformed, membrane-associatedIL-12 p70 stores are released within minutes after in vitroor in vivo contact with Leishmania donovani, an intracellularpathogen. Our findings highlight a novel source of bioactiveIL-12 that is readily available for the rapid initiation ofTh1 host responses to pathogens such as Leishmania species.

Key Words: IL-12 p70, dendritic cells, Th1/Th2, Leishmania, membrane

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