Effects of the two varieties of Cryptococcus neoformans cells and culture filtrate antigens on neutrophil locomotion

Abstract

Cryptococcus neoformans vat. gattii (serotype B and C) isolates have a relative predilection for immunocompetent hosts, and C. neoformans vat. neoformans (serotype A and D) isolates have a relative predilection for immunocompromised hosts, suggesting that normal host resistance tn the former may be relatively inefficient compared with that to the latter variety. In order to assess the possibility that normal cellular host defense is inadequate in protecting against C. neoformans var. gattii, we compared the two varieties of C. neoformans cells and their culture filtrate antigens (CneF) with respect to effects on neutrophil (polymorphonuclear leukocyte [PMN]) locomotion. In a 48-well modified Boyden chamber, the cells and Cnef of C. neoformans vat. neoformans (serotype A and D) isolates stimulated chemotaxis and chemokinesis of human PMN and activated a complement component(s) in pooled human serum tn become a chemoattractant(s) for human PMN. In contrast, the cells and CneF of C. neoformans vat. gattii (serotype B and C) isolates did not stimulate chemotaxis or chemokinesis in human PMN but rather inhibited chemokinesis and chemotactic responses of PMN to pooled human serum and formylmethionyl leucyl phenylalanine. Neither of the CneF from the C. neoformans vat. gattii isolates was cytotoxic tn PMN. Furthermore, with the mouse model, we found that Cnef from C. neoformans vat. neoformans caused migration of PMN into gelatin sponges implanted in naive and immunized mice, whereas CneF from C. neoformans vat. gattii inhibited PMN migration into sponges. Our results, combined with findings of others showing reduced PMN infiltration in lungs of mice infected with C. neofomans var. gattii compared with PMN infiltration in lungs of mice infected with C. neoformans vat. neoformans, indicate that the relative inadequacy of normal host resistance mechanisms to prevent infection with C. neoformans var. gattii results, in part, from inhibition of PMN migration to the site of the organism.