Non-serum-dependent chemotactic factors produced by Candida albicans stimulate chemotaxis by binding to the formyl peptide receptor on neutrophils and to an unknown receptor on macrophages

Serum-free culture filtrates of six Candida species and Saccharomyces cerev isiae were found to contain chemoattractants for human polymorphonuclear le ukocytes (PMNs) and a mouse macrophage-like cell line, J774. The chemotacti c factors differed for the PMN and J774 cells, however, in terms of heat st ability, kinetics of liberation by the yeast cells, and divalent cation req uirements for production. The chemoattractant in Candida albicans culture f iltrates appeared to act through the formyl peptide receptor (FPR) of PMNs, since it was found to induce chemotaxis of Chinese hamster ovary (CHO) cel ls that were expressing the human FPR but did not induce chemotaxis of wild -type CHO cells. The C. albicans culture filtrates also induced migration o f PMNs across confluent monolayers of a human gastrointestinal epithelial c ell line, T84; migration occurred in the basolateral-to-apical direction bu t not the reverse direction, unless the epithelial tight junctions were dis rupted. J774 cells did not migrate toward the formylated peptide (fMet-Leu- Phe; fMLF), and chemotaxis toward the C. albicans culture filtrate was not inhibited by an FPR antagonist (t-butoxycarbunyl-Met-Leu-Phe), suggesting t hat a different receptor mediated J774 cell chemotaxis. In conclusion, we h ave identified a receptor by which a non-serum-dependent chemotactic factor (NSCF) produced by C. albicans induced chemotaxis of PMNs, Additionally, w e have shown that NSCF was active across epithelial monolayers. These findi ngs suggest that NSCFs produced by C. albicans and other yeast species may influence host-pathogen interactions at the gastrointestinal tract mucosal surface by inducing phagocytic-cell infiltration.