In vitro interactions of Candida parapsilosis wild type and lipase deficient mutants with human monocyte derived dendritic cells

BMC Microbiology

Attila Gácser¹  Csaba Vágvölgyi¹  Zsuzsanna Hamari¹  Tibor Németh¹  Kata Filkor²  István Nagy² 

[1] Department of Microbiology, University of Szeged, Közép fasor 52, H-6726 Szeged, Hungary;Institute for Plant Genomics, Human Biotechnology and Bioenergy, Bay Zoltán Foundation for Applied Research, Derkovits fasor 2., 6726 Szeged, Hungary

关键词: secreted lipase;    innate immunity;    dendritic cell;    Candida;   

Others  :  1223683
DOI  :  10.1186/1471-2180-11-122

 received in 2011-01-18, accepted in 2011-05-29,  发布年份 2011

【 摘 要 】

Background

Candida parapsilosis typically is a commensal of human skin. However, when host immune defense is compromised or the normal microflora balance is disrupted, C. parapsilosis transforms itself into an opportunistic pathogen. Candida-derived lipase has been identified as potential virulence factor. Even though cellular components of the innate immune response, such as dendritic cells, represent the first line of defense against invading pathogens, little is known about the interaction of these cells with invading C. parapsilosis. Thus, the aim of our study was to assess the function of dendritic cells in fighting C. parapsilosis and to determine the role that C. parapsilosis-derived lipase plays in the interaction with dendritic cells.

Results

Monocyte-derived immature and mature dendritic cells (iDCs and mDCs, respectively) co-cultured with live wild type or lipase deficient C. parapsilosis strains were studied to determine the phagocytic capacity and killing efficiency of host cells. We determined that both iDCs and mDCs efficiently phagocytosed and killed C. parapsilosis, furthermore our results show that the phagocytic and fungicidal activities of both iDCs and mDCs are more potent for lipase deficient compared to wild type yeast cells. In addition, the lipase deficient C. parapsilosis cells induce higher gene expression and protein secretion of proinflammatory cytokines and chemokines in both DC types relative to the effect of co-culture with wild type yeast cells.

Conclusions

Our results show that DCs are activated by exposure to C. parapsilosis, as shown by increased phagocytosis, killing and proinflammatory protein secretion. Moreover, these data strongly suggest that C. parapsilosis derived lipase has a protective role during yeast:DC interactions, since lipase production in wt yeast cells decreased the phagocytic capacity and killing efficiency of host cells and downregulated the expression of host effector molecules.

【 授权许可】

   
2011 Nagy et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]van Asbeck EC, Clemons KV, Stevens DA: Candida parapsilosis: a review of its epidemiology, pathogenesis, clinical aspects, typing and antimicrobial susceptibility. Crit Rev Microbiol 2009, 35:283-309.
• [2]Pfaller MA, Jones RN, Doern GV, Fluit AC, Verhoef J, Sader HS, Messer SA, Houston A, Coffman S, Hollis RJ: International surveillance of blood stream infections due to Candida species in the European SENTRY Program: species distribution and antifungal susceptibility including the investigational triazole and echinocandin agents. SENTRY Participant Group (Europe). Diagn Microbiol Infect Dis 1999, 35:19-25.
• [3]Trofa D, Gacser A, Nosanchuk JD: Candida parapsilosis, an emerging fungal pathogen. Clin Microbiol Rev 2008, 21:606-625.
• [4]Pfaller MA, Moet GJ, Messer SA, Jones RN, Castanheira M: Candida Bloodstream Infections: Comparison of Species Distribution and Antifungal Resistance in Community Onset and Nosocomial Isolates in the SENTRY Antimicrobial Surveillance Program (2008-2009). Antimicrob Agents Chemother 2010.
• [5]Clark TA, Slavinski SA, Morgan J, Lott T, Arthington-Skaggs BA, Brandt ME, Webb RM, Currier M, Flowers RH, Fridkin SK, Hajjeh RA: Epidemiologic and molecular characterization of an outbreak of Candida parapsilosis bloodstream infections in a community hospital. J Clin Microbiol 2004, 42:4468-4472.
• [6]Clerihew L, Lamagni TL, Brocklehurst P, McGuire W: Candida parapsilosis infection in very low birthweight infants. Arch Dis Child Fetal Neonatal Ed 2007, 92:F127-129.
• [7]Benjamin DK Jr, Garges H, Steinbach WJ: Candida bloodstream infection in neonates. Semin Perinatol 2003, 27:375-383.
• [8]Smith PB, Steinbach WJ, Benjamin DK Jr: Neonatal candidiasis. Infect Dis Clin North Am 2005, 19:603-615.
• [9]Newman SL, Holly A: Candida albicans is phagocytosed, killed, and processed for antigen presentation by human dendritic cells. Infect Immun 2001, 69:6813-6822.
• [10]Pivarcsi A, Bodai L, Rethi B, Kenderessy-Szabo A, Koreck A, Szell M, Beer Z, Bata-Csorgoo Z, Magocsi M, Rajnavolgyi E, Dobozy A, Kemeny L: Expression and function of Toll-like receptors 2 and 4 in human keratinocytes. Int Immunol 2003, 15:721-730.
• [11]Netea MG, Brown GD, Kullberg BJ, Gow NA: An integrated model of the recognition of Candida albicans by the innate immune system. Nat Rev Microbiol 2008, 6:67-78.
• [12]Neumann AK, Jacobson K: A novel pseudopodial component of the dendritic cell anti-fungal response: the fungipod. PLoS Pathog 2010, 6:e1000760.
• [13]Gacser A, Trofa D, Schafer W, Nosanchuk JD: Targeted gene deletion in Candida parapsilosis demonstrates the role of secreted lipase in virulence. J Clin Invest 2007, 117:3049-3058.
• [14]Gacser A, Stehr F, Kroger C, Kredics L, Schafer W, Nosanchuk JD: Lipase 8 affects the pathogenesis of Candida albicans. Infect Immun 2007, 75:4710-4718.
• [15]Netea MG, Gijzen K, Coolen N, Verschueren I, Figdor C, Van der Meer JW, Torensma R, Kullberg BJ: Human dendritic cells are less potent at killing Candida albicans than both monocytes and macrophages. Microbes Infect 2004, 6:985-989.
• [16]Shao X, Mednick A, Alvarez M, van Rooijen N, Casadevall A, Goldman DL: An innate immune system cell is a major determinant of species-related susceptibility differences to fungal pneumonia. J Immunol 2005, 175:3244-3251.
• [17]Zaragoza O, Alvarez M, Telzak A, Rivera J, Casadevall A: The relative susceptibility of mouse strains to pulmonary Cryptococcus neoformans infection is associated with pleiotropic differences in the immune response. Infect Immun 2007, 75:2729-2739.
• [18]Colonna M, Pulendran B, Iwasaki A: Dendritic cells at the host-pathogen interface. Nat Immunol 2006, 7:117-120.
• [19]Gacser A, Salomon S, Schafer W: Direct transformation of a clinical isolate of Candida parapsilosis using a dominant selection marker. FEMS Microbiol Lett 2005, 245:117-121.
• [20]Eissenberg LG, Goldman WE, Schlesinger PH: Histoplasma capsulatum modulates the acidification of phagolysosomes. J Exp Med 1993, 177:1605-1611.
• [21]Shi L, Albuquerque PC, Lazar-Molnar E, Wang X, Santambrogio L, Gacser A, Nosanchuk JD: A monoclonal antibody to Histoplasma capsulatum alters the intracellular fate of the fungus in murine macrophages. Eukaryot Cell 2008, 7:1109-1117.
• [22]Fernandez-Arenas E, Bleck CK, Nombela C, Gil C, Griffiths G, Diez-Orejas R: Candida albicans actively modulates intracellular membrane trafficking in mouse macrophage phagosomes. Cell Microbiol 2009, 11:560-589.
• [23]Marcil A, Gadoury C, Ash J, Zhang J, Nantel A, Whiteway M: Analysis of PRA1 and its relationship to Candida albicans- macrophage interactions. Infect Immun 2008, 76:4345-4358.
• [24]Lazzaro BP, Rolff J: Immunology. Danger, microbes, and homeostasis. Science 2011, 332:43-44.
• [25]Matzinger P: The danger model: a renewed sense of self. Science 2002, 296:301-305.
• [26]Strieter RM, Kunkel SL, Showell HJ, Remick DG, Phan SH, Ward PA, Marks RM: Endothelial cell gene expression of a neutrophil chemotactic factor by TNF-alpha, LPS, and IL-1 beta. Science 1989, 243:1467-1469.
• [27]Liu AY, Destoumieux D, Wong AV, Park CH, Valore EV, Liu L, Ganz T: Human beta-defensin-2 production in keratinocytes is regulated by interleukin-1, bacteria, and the state of differentiation. J Invest Dermatol 2002, 118:275-281.