Early differential molecular response of a macrophage cell line to yeast and hyphal forms of Candida albicans.
The dimorphic transition of Candida albicans from the yeast (Y-Candida) to the hyphal (H-Candida) form is a complex event; the relevance of this transition in fungal pathogenicity is still poorly understood. By using a cloned macrophage cell line (ANA-1), we questioned whether the interaction between macrophages and Y-Candida or H-Candida could affect specific cell functions, i.e., tumor necrosis factor and lysozyme production. We found that ANA-1 macrophages selectively responded to H-Candida with increased tumor necrosis factor and downregulated lysozyme, as assessed by measurement of relative mRNA levels and secreted biological activities. The H-Candida-mediated effects were (i) dependent upon the ratio between ANA-1 macrophages and H-Candida, (ii) detectable after 1 h of coincubation, and (iii) accomplished without fungal ingestion. Conversely, Y-Candida, which was found inside the ANA-1 macrophages, did not affect tumor necrosis factor and lysozyme production, nor did it prevent the macrophage response to other stimuli. Overall, these results indicate that a macrophage can distinguish between Y-Candida and H-Candida and that only the latter is able to modulate specific functions. H-Candida is recognized and probably processed as an extracellular target. The possible implication of macrophages as autocrine and paracrine regulatory cells during Candida infections is discussed.
Blasi
E
E
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
Pitzurra
L
L
Puliti
M
M
Lanfrancone
L
L
Bistoni
F
F
D000818:Animals; D002176:Candida albicans / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009113:Muramidase / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009113:Muramidase