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Infection and Immunity, February 2000, p. 558-563, Vol. 68, No. 2
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Early Induction of Interleukin-12 by Human Monocytes Exposed to Cryptococcus neoformans Mannoproteins

Lucia Pitzurra,1 Robert Cherniak,2 Monica Giammarioli,1 Stefano Perito,1 Francesco Bistoni,1 and Anna Vecchiarelli1,*

Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, 06122 Perugia, Italy,1 and Department of Chemistry, Georgia State University, Atlanta, Georgia 303032

Received 26 May 1999/Returned for modification 16 July 1999/Accepted 6 October 1999

Interleukin-12 (IL-12) production by human monocytes stimulated with mannoproteins (MPs) of Cryptococcus neoformans was investigated. The results reported show that secreted or cell-associated MPs induce an early and significant production of IL-12. MPs show different capabilities to quantitatively affect IL-12 production; MP2, an 8.2-kDa MP purified from the culture supernatant of C. neoformans, appears to be the most potent stimulator. Cytochalasin B inhibits both internalization and IL-12 induction by MP. In addition, a drastic reduction of IL-12 was observed when monocytes were cultured in the absence of normal human serum or treated with soluble mannan. Early production of IL-12 promotes early secretion of gamma interferon by T cells but does not influence the magnitude of the MP-induced lymphoproliferative response. Overall our results identify cryptococcal antigens responsible for rapid and potent induction of IL-12 in monocytes. MPs appear to regulate IL-12 secretion by internalization via the endocytic pathway and by interaction with monocyte receptors or serum factors.

* Corresponding author. Mailing address: Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Via del Giochetto, 06122 Perugia, Italy. Phone and fax: 39-075-585-3407. E-mail: vecchiar{at}unipg.it.

Infection and Immunity, February 2000, p. 558-563, Vol. 68, No. 2
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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