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Clinical and Diagnostic Laboratory Immunology, November 2002, p. 1282-1294, Vol. 9, No. 6
1071-412X/02/$04.00+0     DOI: 10.1128/CDLI.9.6.1282-1294.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

NK Cells Mediate Increase of Phagocytic Activity but Not of Proinflammatory Cytokine (Interleukin-6 [IL-6], Tumor Necrosis Factor Alpha, and IL-12) Production Elicited in Splenic Macrophages by Tilorone Treatment of Mice during Acute Systemic Candidiasis

José Juan Gaforio,* Elena Ortega, Ignacio Algarra, María José Serrano, and Gerardo Alvarez de Cienfuegos

Microbiology Unit, Department of Health Sciences, Faculty of Experimental Sciences, University of Jaén, 23071 Jaén, Spain

Received 17 April 2002/ Returned for modification 5 June 2002/ Accepted 9 August 2002

The participation of NK cells in the activation of splenic macrophages or in resistance to systemic candidiasis is still a matter of debate. We had previously reported that there is a correlation between natural killer cell activation and resistance to systemic candidiasis. In those experiments we had used tilorone to boost NK cell activity in mice. Here we show a mechanism elicited by tilorone in splenic macrophages which could explain their effect on mouse survival during acute disseminated Candida albicans infection. The results demonstrate that tilorone treatment elicits, by a direct effect, the production of proinflammatory cytokines (interleukin-6 [IL-6], tumor necrosis factor alpha [TNF-{alpha}], and IL-12) by splenic macrophages. In addition, it increases the capacity of splenic macrophages to phagocytize C. albicans through activation of NK cells. We also demonstrate that the presence of NK cells is essential for maintaining a basal level of phagocytic activity, which characterizes splenic macrophages of naïve control mice. The results demonstrate that it is possible to identify two phenotypically and functionally peculiar cell populations among splenic macrophages: (i) cells of the "stimulator/secretor phenotype," which show high levels of major histocompatibility complex (MHC) class II surface expression, are poorly phagocytic, and synthesize the proinflammatory cytokines IL-6, TNF-{alpha}, and IL-12, and (ii) cells of the "phagocytic phenotype," which express low levels of MHC class II molecules, are highly phagocytic, and do not secrete proinflammatory cytokines.


* Corresponding author. Mailing address: Microbiology Unit, Department of Health Sciences, Faculty of Experimental Sciences, University of Jaén, Campus Las Lagunillas s/n, 23071 Jaén, Spain. Phone: 34-953-012-002. Fax: 34-953-012-141. E-mail: jgaforio{at}ujaen.es.


Clinical and Diagnostic Laboratory Immunology, November 2002, p. 1282-1294, Vol. 9, No. 6
1071-412X/02/$04.00+0     DOI: 10.1128/CDLI.9.6.1282-1294.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.