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Invasive Aspergillosis: New Approaches against a Dangerous Fungal Infection

Invasive Aspergillosis
Reported by
Marilynn Larkin

Posted April 03, 2007


Invasive aspergillosis is the most common filamentous fungal infection observed in immunocompromised patients and is a leading cause of fungal mortality. The December 14, 2006, symposium at the Academy brought together five leading clinical and research experts to discuss the issue.

David W. Denning of the University Of Manchester and Wythenshawe Hospital, UK, provided an overview of the three main types of aspergillosis, the culprit pathogens, and the challenges facing clinicians and researchers attempting to thwart the disease course. Kieren A. Marr of the Fred Hutchinson Cancer Research Center and University of Washington in Seattle provided an assessment of currently available Aspergillus diagnostics. Thomas J. Walsh of the National Cancer Institute reviewed of environmental interventions to curb aspergillosis and the benefits and limitations of currently available therapies. Jean-Paul Latgé of the Pasteur Institut in Paris and Gordon Brown of the University of Cape Town offered perspectives on the interaction of Aspergillus with the immune system.

Web Sites

The Aspergillus Website
This Web site managed by David Denning includes a wealth of both scientific and medical information, and other resources related to aspergillosis.

Journal Articles

Clinical Perspective and Research Challenges

Arendrup MC, O'Driscoll BR, Petersen E, Denning DW. 2006. Acute pulmonary aspergillosis in immunocompetent subjects after exposure to bark chippings. Scand. J. Infect Dis. 38: 945-949.

Crosdale D, Poulton K, Ollier W, et al. 2001. Mannose binding lectin gene polymorphisms as a susceptibility factor for chronic necrotising pulmonary aspergillosis. J. Infect. Dis. 184: 653-656.

Denning DW. 2004. Aspergillosis in "nonimmunocompromised" critically ill patients. Am. J. Respir. Crit. Care Med. 170: 580-581.

Denning DW. 2003. Echinocandin antifungal drugs. Lancet 362: 1142-1151.

Denning DW, Marr KA, Lau WM, et al. 2006. Micafungin (FK463), alone or in combination with other systemic antifungal agents, for the treatment of acute invasive aspergillosis. J. Infect. 53: 337-349.

Denning DW, O'Driscoll BR, Hogaboam CM, et al. 2006. The link between fungi and severe asthma: a summary of the evidence. Eur. Resp. J. 27: 615-626.

Denning DW, Riniotis K, Dobrashian R, Sambatakou H. 2003. Chronic cavitary and fibrosing pulmonary and pleural aspergillosis: case series, proposed nomenclature change, and review. Clin. Infect. Dis. 37 Suppl 3: S265-280.

Galagan JE, Calvo SE, Cuomo C, et al. 2005. Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae. Nature 438: 1105-1115.

Greene RE, Schlamm HT, Oestmann JW, et al. 2007. Imaging findings in acute invasive pulmonary aspergillosis: clinical significance of the halo sign. Clin. Infect. Dis. 44: 373-379.

Herbrecht R, Denning DW, Patterson TF, et al. 2002. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N. Engl. J. Med. 347: 408-415.

Howard SJ, Webster I, Moore CB, et al. 2006. Multi-azole resistance in Aspergillus fumigatus. Int. J. Antimicrob. Agents 28: 450-453.

Jain LR, Denning DW. 2006. The efficacy and tolerability of voriconazole in the treatment of chronic cavitary pulmonary aspergillosis. J. Infect. 52: e133-137.

Keevil B, Newman, Lockhart S, et al. 2004. Validation of an assay for voriconazole in serum samples using liquid chromatography-tandem mass spectrometry. Ther. Drug Monit. 26: 650-657.

Mabey JE, Anderson MJ, Giles P, et al. 2004. CADRE: the Central Aspergillus Data Repository. Nucleic Acids Res. 32: D401-D405. Full Text

Machida M, Asai K, Sano M, et al. 2005. Genome sequencing and analysis of Aspergillus oryzae. Nature 438: 1157-1161.

Maertens J, Raad I, Petrikkos G, et al. 2004. Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy. Clin. Infect. Dis. 39: 1563-1571.

Nierman W, Pain A, Anderson MJ, et al. 2005. Genomic sequence of the pathogenic and allergenic Aspergillus fumigatus. Nature 438: 1151-1156.

O'Driscoll BR, Hopkinson LC, Denning DW. 2005. Mold sensitization is common amongst patients with severe asthma requiring multiple hospital admissions. BMC Pulmonary Medicine 5: 4. Full Text

Paisley D, Robson GD, Denning DW. 2005. Correlation between in vitro growth rate and in vivo virulence in Aspergillus fumigatus. Med. Mycol. 43: 397-401.

Paoletti M, Rydholm C, Schwier E, et al. 2005. Evidence for sexuality in the opportunistic fungal pathogen Aspergillus fumigatus. Curr. Biol. 15: 1242-1248.

Patterson TF, Boucher HW, Herbrecht R, et al. 2005. Strategy of following voriconazole versus amphotericin B therapy with otherlicensed antifungal therapy for primary treatment of invasive aspergillosis: impact of other therapies on outcome. Clin. Infect. Dis. 41: 1448-1452.

Sambatakou H, Dupont B, Lode H, Denning DW. Voriconazole treatment for subacute invasive and chronic pulmonary aspergillosis. Am. J. Med. 119: 527.e17-24.

Sambatakou H, Pravica V, Hutchinson I, Denning DW. 2006. Cytokine profiling of pulmonary aspergillosis. Int. J. Immunogenetics 33: 297-302.

Steinbach WJ, Stevens DA, Denning DW. 2003. Combination and sequential antifungal therapy for invasive aspergillosis: review of published in vitro and in vivo interactions and 6281 clinical cases from 1966 to 2001. Clin. Infect. Dis. 37 Suppl 3: S188-224.

Stevens DA, Moss RB, Kurup VP, et al. 2003. Allergic bronchopulmonary aspergillosis in cystic fibrosis—state of the art: Cystic Fibrosis Foundation Consensus Conference. Clin. Infect. Dis. 37 Suppl 3: S225-264.

Woodcock AA, Steele N, Moore CB, et al. 2006. Fungal contamination of bedding. Allergy 61: 140-142.

Zaspel U, Denning DW, Lemke AJ, et al. 2004. Diagnosis of IPA in HIV: the role of the chest X-ray and radiologist. Eur. Radiol. 14: 2030-2037.

Diagnostics: State of the Art

Balajee SA, Weaver M, Imhof A, Marr KA. 2004. Aspergillus fumigatus variant with decreased susceptibilities to multiple antifungals. Antimicrob. Agents Chemother. 48: 1197-1203. Full Text

Marr KA, Balajee SA, Hawn TR, et al. 2003. Differential role of MyD88 in macrophage-mediated responses to opportunistic fungal pathogens. Infect. Immun. 71: 5280-5286. Full Text

Marr KA, Balajee SA, Leisenring W, et al. 2004. Detection of galactomannan antigenemia by enzyme immunoassay for the diagnosis of invasive aspergillosis: variables that affect performance. J. Infect. Dis. 190: 641-649.

Marr KA, Carter RA, Boeckh M, et al. 2002. Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risks. Blood 10: 4358-4366. Full Text

Marr KA, Crippa F, Leisenring W, et al. 2004. Itraconazole versus fluconazole for antifungal prophylaxis in allogeneic HSCT patients. Blood 103: 1527-1533. Full Text

Therapy: State of the Art

Anaissie EJ, Stratton SL, Dignani MC, et al. 2003. Pathogenic molds (including Aspergillus species) in hospital water distribution systems: a 3-year prospective study and clinical implications for patients with hematologic malignancies. Blood 101: 2542-2546. Full Text

Antachopoulos C, Walsh TJ. 2005. New agents for invasive mycoses in children. Curr. Opin. Pediatr. 17: 78-87.

Benjamin DK, Driscoll T, Seibel NL, et al. 2006. Safety and pharmacokinetics of intravenous anidulafungin in children with neutropenia at high risk for invasive fungal infections. Antimicrob. Agents Chemother. 50: 632-638. Full Text

Boucher HW, Groll AH, Chiou CC, Walsh TJ. 2004. Newer systemic antifungal agents: pharmacokinetics, safety, and efficacy. Drugs 64: 1997-2020.

Chu JH, Feudtner C, Heydon K, et al. 2006. Hospitalizations for endemic mycoses: a population-based national study. Clin. Infect. Dis. 42: 822-825.

Cortez KJ, Lyman CA, Kottilil S, et al. 2006. Functional genomics of innate host defense molecules in normal human monocytes in response to Aspergillus fumigatus. Infect. Immun. 74: 2353-2365. Full Text

De Lucca AJ, Bland JM, Boue S, et al. 2006. Synergism of CAY-1 with Amphotericin B and Itraconazole. Chemotherapy 52: 285-287.

Dennis CG, Greco WR, Brun Y, et al. 2006. Effect of amphotericin B and micafungin combination on survival, histopathology, and fungal burden in experimental aspergillosis in the p47phox−/− mouse model of chronic granulomatous disease. Antimicrob. Agents Chemother. 50: 422-427. Full Text

Dignani MC, Rex JH, Chan KW, et al. 2005. Immunomodulation with interferon-γ and colony-stimulating factors for refractory fungal infections in patients with leukemia. Cancer 104: 199-204.

Dotis J, Simitsopoulou M, Dalakiouridou M, et al. 2006. Effects of lipid formulations of amphotericin B on activity of human monocytes against Aspergillus fumigatus. Antimicrob. Agents Chemother. 50: 868-873.

El Saleeby CM, Allison KJ, Knapp KM, et al. 2005. Discordant rise in galactomannan antigenemia in a patient with resolving Aspergillosis, renal failure, and ongoing hemodialysis. J. Clin. Microbiol. 43: 3560-3563. Full Text

Espinel-Ingroff A, Fothergill A, Ghannoum M, et al. 2005. Quality control and reference guidelines for CLSI broth microdilution susceptibility method (M 38-A document) for amphotericin B, itraconazole, posaconazole, and voriconazole. J. Clin. Microbiol. 43: 5243-5246. Full Text

Francesconi A, Kasai M, Petraitiene R, et al. 2006. Characterization and comparison of galactomannan enzyme immunoassay and quantitative real-time PCR assay for detection of Aspergillus fumigatus in bronchoalveolar lavage fluid from experimental invasive pulmonary Aspergillosis. J. Clin. Microbiol. 44: 2475-2480. Full Text

Gil-Lamaignere C, Winn RM, Simitsopoulou M, et al. 2005. Inteferon-γ and granulocyte-macrophage colony-stimulating factor augment the antifungal activity of human polymorphonuclear leukocytes against Scedosporium spp.: comparison with Aspergillus spp. Med. Mycol. 43: 253-260.

Groll AH, Lyman CA, Petraitis V, et al. 2006. Compartmentalized intrapulmonary pharmacokinetics of amphotericin B and its lipid formulations. Antimicrob. Agents Chemother. 50: 3418-23. Full Text

Groll AH, Mickiene D, Petraitis V, et al. 2005. Compartmental pharmacokinetics and tissue distribution of the antifungal triazole ravuconazole following intravenous administration of its di-lysine phosphoester prodrug (BMS-379224) in rabbits. J. Antimicrob. Chemother. 56: 899-907. Full Text

Groll AH, Stergiopoulou T, Roilides E, Walsh TJ. 2005. Micafungin: pharmacology, experimental therapeutics and clinical applications. Expert. Opin. Investig. Drugs 14: 489-509.

Groll AH, Walsh TJ. 2006. Antifungal efficacy and pharmacodynamics of posaconazole in experimental models of invasive fungal infections. Mycoses 49 Suppl 1: 7-16.

Groll AH, Walsh TJ. 2005. Posaconazole: clinical pharmacology and potential for management of fungal infections. Expert Rev. Anti. Infect. Ther. 3: 467-487.

Hope WW, Walsh TJ, Denning DW. 2005. The invasive and saprophytic syndromes due to Aspergillus spp. Med. Mycol. 43 Suppl 1: S207-238.

Hope WW, Walsh TJ, Denning DW. 2005. Laboratory diagnosis of invasive aspergillosis.Lancet Infect. Dis. 5: 609-622.

La Via WV, Lambert JL, Pelletier MJ, et al. 2006. Measurement of amphotericin B concentration by resonant Raman spectroscopy—a novel technique that may be useful for non-invasive monitoring. Med. Mycol. 44: 169-174.

Maertens J, Raad I, Petrikkos G, et al. 2004. Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy. Clin. Infect. Dis. 39: 1563-1571.

Marr KA, Balajee SA, McLaughlin L, et al. 2004. Detection of galactomannan antigenemia by enzyme immunoassay for the diagnosis of invasive aspergillosis: variables that affect performance. J. Infect. Dis. 190: 641-649.

Meletiadis J, Petraitis V, Petraitiene R, et al. 2006. Triazole-polyene antagonism in experimental invasive pulmonary aspergillosis: in vitro and in vivo correlation. J. Infect. Dis. 194: 1008-18.

Morgan J, Wannemuehler KA, Marr KA, et al. 2005. Incidence of invasive aspergillosis following hematopoietic stem cell and solid organ transplantation: interim results of a prospective multicenter surveillance program. Med. Mycol. 43 Suppl 1: S49-58.

O'Sullivan CE, Kasai M, Francesconi A, et al. 2003. Development and validation of a quantitative real-time PCR Assay using fluorescence resonance energy transfer (FRET) technology for detection of Aspergillus fumigatus in experimental invasive pulmonary aspergillosis. J. Clin. Microbiol. 41: 5676-5682. Full Text

Panicker J, Walsh T, Kamani N. 2006. Recurrent central nervous system blastomycosis in an immunocompetent child treated successfully with sequential liposomal amphotericin B and voriconazole. Pediatr. Infect. Dis. J. 25: 377-379.

Pannaraj PS, Walsh TJ, Baker CJ. 2005. Advances in antifungal therapy. Pediatr. Infect. Dis. J. 24: 921-922.

Peter J, Armstrong D, Lyman CA, Walsh TJ. 2005. Use of fluorescent probes to determine MICs of amphotericin B and caspofungin against Candida spp. and Aspergillus spp. J. Clin. Microbiol. 43: 3788-3792. Full Text

Petraitiene R, Petraitis V, Lyman CA, et al. 2004. Efficacy, safety, and plasma pharmacokinetics of escalating dosages of intravenously administered ravuconazole lysine phosphoester for treatment of experimental pulmonary aspergillosis in persistently neutropenic rabbits. Antimicrob. Agents Chemother. 48: 1188-1196. Full Text

Petraitis V, Petraitiene R, Lin P, et al. 2005. Efficacy and safety of generic amphotericin B in experimental pulmonary aspergillosis. Antimicrob. Agents Chemother. 49: 1642-5, 2005. Full Text

Petraitis V, Petraitiene R, Solomon J, et al. 2006. Multidimensional volumetric imaging of pulmonary infiltrates for measuring therapeutic response to antifungal therapy in experimental invasive pulmonary aspergillosis. Antimicrob. Agents Chemother. 50: 1510-1517. Full Text

Segal BH, Kwon-Chung J, Walsh TJ, et al. 2006. Immunotherapy for fungal infections. Clin. Infect. Dis. 42: 507-515.

Segal BH, Walsh TJ. 2006. Current approaches to diagnosis and treatment of invasive aspergillosis. Am. J. Respir. Crit. Care Med. 173: 707-717.

Steinbach WJ, Benjamin DK, Kontoyiannis DP, et al. 2004. Infections due to Aspergillus terreus: a multicenter retrospective analysis of 83 cases. Clin. Infect. Dis. 39: 192-198.

Steinbach WJ, Perfect JR, Schell WA, et al. 2004. In vitro analyses, animal models, and 60 clinical cases of invasive Aspergillus terreus infection. Antimicrob. Agents Chemother. 48: 3217-3225. Full Text

Steinbach WJ, Walsh TJ. 2006. Mycoses in pediatric patients. Infect. Dis. Clin. North Am. 20: 663-78.

Walsh TJ, Adamson PC, Seibel NL, et al. 2005. Pharmacokinetics, safety, and tolerability of caspofungin in children and adolescents. Antimicrob. Agents Chemother. 49: 4536-4545. Full Text

Walsh TJ, Groll A, Hiemenz J, et al. 2004. Infections due to emerging and uncommon medically important fungal pathogens. Clin. Microbiol. Infect. 10 Suppl 1: 48-66.

Walsh TJ, Petraitis V, Petraitiene R, et al. 2003. Experimental pulmonary aspergillosis due to Aspergillus terreus: pathogenesis and treatment of an emerging fungal pathogen resistant to amphotericin B. J. Infect. Dis. 188: 305-319.

Walsh TJ, Roilides E, Cortez K, et al. 2005. Control, immunoregulation, and expression of innate pulmonary host defenses against Aspergillus fumigatus. Med. Mycol. 43 Suppl 1: S165-172.

Wiley JM, Seibel NL, Walsh TJ. 2005. Efficacy and safety of amphotericin B lipid complex in 548 children and adolescents with invasive fungal infections. Pediatr. Infect. Dis. J. 24: 167-174.

Winn RM, Gil-Lamaignere C, Roilides E, et al. 2003. Selective effects of interleukin (IL)-15 on antifungal activity and IL-8 release by polymorphonuclear leukocytes in response to hyphae of Aspergillus species. J. Infect. Dis. 188: 585-590.

Zaoutis TE, Heydon K, Chu JH, et al. 2006. Epidemiology, outcomes, and costs of invasive aspergillosis in immunocompromised children in the United States, 2000. Pediatrics 117: e711-716. Full Text

Cell Wall, Antigens, and Virulence

Balloy V, Huerre M, Latgé JP, Chignard M. 2005. Differences in patterns of infection and inflammation for corticosteroid treatment and chemotherapy in experimental invasive pulmonary aspergillosis. Infect. Immun. 73: 494-503. Full Text

Balloy V, Si-Tahar M, Takeuchi O, et al. 2005. Involvement of toll-like receptor 2 in experimental invasive pulmonary aspergillosis. Infect. Immun. 73: 5420-5425. Full Text

Beauvais A, Maubon D, Park S, et al. 2005. Two α(1-3) glucan synthases with different functions in Aspergillus fumigatus. Appl. Environ. Microbiol. 71: 1531-1538. Full Text

Braedel S, Radsak M, Einsele H, et al. 2004. Aspergillus fumigatus antigens activate innate immune cells via toll-like receptors 2 and 4. Br. J. Haematol. 125: 392-399.

Chabane S, Sarfati J, Ibrahim-Granet O, et al. 2006. Glycosylphosphatidylinositol-anchored Ecm33p influences conidial cell wall biosynthesis in Aspergillus fumigatus. Appl. Environ. Microbiol. 72: 3259-3267. Full Text

Costachel C, Coddeville B, Latgé JP, Fontaine T. 2005. Glycosylphosphatidylinositol-anchored fungal polysaccharide in Aspergillus fumigatus. J. Biol. Chem. 280: 39,835-39,842. Full Text

Dubourdeau M, Athman R, Balloy V, et al. 2006. Aspergillus fumigatus induces innate immune responses in alveolar macrophages through the MAPK pathway Independently of TLR2 and TLR4. J. Immunol. 177: 3994-4001.

Dubourdeau M, Athman R, Balloy V, et al. 2006. Interaction of Aspergillus fumigatus with alveolar macrophage. Med. Mycol. 44: S213-S217.

Fontaine T, Smith TK, Crossman A, et al. 2004. In vitro biosynthesis of Glycosylphosphatidylinositol in Aspergillus fumigatus. Biochemistry 43: 15,267-15,275.

Latgé JP, Mouyna I, Tekaia F, et al. 2005. Specific molecular features in the organization and biosynthesis of the cell wall of Aspergillus fumigatus. Med. Mycol. 43: S15-S22.

Maubon D, Park S, Tanguy M, et al. 2006. AGS3, an α(1-3)glucan synthase gene family member of Aspergillus fumigatus, modulates mycelium growth in the lung of experimentally infected mice. Fungal Genet. Biol. 43: 366-375.

Morelle W, Bernard M, Debeaupuis JP, et al. 2005. Galactomannoproteins of Aspergillus fumigatus. Eukaryot. Cell 4: 1308-1316. Full Text

Mouyna I, Morelle W, Vai M, et al. 2005. Deletion of GEL2 encoding for a β(1-3)glucanosyltransferase affects morphogenesis and virulence in Aspergillus fumigatus. Mol. Microbiol. 56: 1675-1688.

Schöbel F, Ibrahim-Granet O, Avé P, et al. 2007. Aspergillus fumigatus does not require fatty acid metabolism via isocitrate lyase for development of invasive aspergillosis. Infect. Immun. 75: 1237-44.

Shibuya K, Paris S, Ando T, et al. 2006. Catalases of Aspergillus fumigatus and inflammation in Aspergillosis. Jap. J. Med. Mycol. 47: 249-255.

Tekaia F, Latgé JP. 2005. Aspergillus fumigatus: saprophyte or pathogen? Curr. Opin. Microbiol. 8: 385-392.

Innate Immunity and Dectin-1

Brown GD. 2006. Dectin-1: a signalling non-TLR pattern-recognition receptor. Nat. Rev. Immunol. 6: 33-43.

Brown GD, Gordon S. 2005. Immune recognition of fungal β-glucans. Cell. Microbiol. 7: 471-479.

Brown GD, Gordon S. 2001. Immune recognition: a new receptor for β-glucans. Nature 413: 36-37.

Brown GD, Herre J, Williams DL, et al. 2003. Dectin-1 mediates the biological effects of β-glucans. J. Exp. Med. 197: 1119-1124. Full Text

Diniz SN, Nomizo R, Cisalpino PS, et al. 2004. PTX3 function as an opsonin for the dectin-1-dependent internalization of zymosan by macrophages. J. Leukoc. Biol. 75: 649-656. Full Text

Gersuk GM, Underhill DM, Shu L, Marr KA. 2006. Dectin-1 and TLRs permit macrophages to distinguish between different Aspergillus fumigatus cellular states. J. Immunol. 176: 3717-3724.

Graham LM, Tsoni SV, Willment J, et al. 2006. Soluble Dectin-1 as a tool to detect β-glucans. J. Immunol. Methods 314: 164-169.

Gross O, Gewies A, Finger K, et al. 2006. Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity. Nature 442: 651-656.

Heinsbroek SEM, Taylor PR, Rosas M, et al. 2006. Expression of functionally different Dectin-1 isoforms by murine macrophages. J. Immunol. 176: 5513-5518.

Herre J, Gordon S, Brown GD. 2004. Dectin-1 and its role in the recognition of β-glucans by macrophages. Mol. Immunol. 40: 869-876.

Herre J, Gordon S, Brown GD. 2004. The role of dectin-1 in antifungal immunity. Crit. Rev. Immunol. 24: 193-204.

Herre J, Marshall ASJ, Caron E, et al. 2004. Dectin-1 utilizes novel mechanisms for yeast phagocytosis in macrophages. Blood 104: 4038-4045. Full Text

Kennedy AD, Willment JA, Dorward DW, et al. 2007. Dectin-1 promotes fungicidal activity of human neutrophils. Eur. J. Immunol. 37: 467-78.

Ozment-Skelton TR, Goldman MP, Gordon S, et al. 2006. Prolonged reduction of leukocyte membrane associated Dectin-1 levels following β-glucan administration. J. Pharmacol. Exp. Ther. 318: 540-546.

Palma AS, Feizi T, Zhang Y, et al. 2006. Ligands for the β-glucan receptor, Dectin-1, assigned using "designer" microarrays of oligosaccharide probes (neoglycolipids) generated from glucan polysaccharides. J. Biol. Chem. 281: 5771-5779. Full Text

Rogers NC, Slack EC, Edwards AD, et al. 2005. Syk-dependent cytokine induction by dectin-1 reveals a novel pattern recognition pathway for C-type lectins. Immunity 22: 507-517.

Steele C, Rapaka R, Metz A, et al. 2005. The β-glucan receptor dectin-1 recognizes specific morphologies of Aspergillus fumigatus. PLoS Pathogens 1: e42. Full Text

Suram S, Brown GD, Ghosh M, et al. 2006. Regulation of cytosolic phospholipase A2 activation and cyclooxygenase 2 expression in macrophages by the β-glucan receptor. J. Biol. Chem. 281: 5506-5514. Full Text

Taylor PR, Brown GD, Reid DM, et al. 2002. The β-glucan receptor, Dectin-1, is predominantly expressed on the surface of cells of the monocyte/macrophage and neutrophil lineages. J. Immunol. 169: 3876-3882 Full Text

Willment JA, Lin HH, Reid DM, et al. 2003. Dectin-1 expression and function is enhanced on alternatively activated and GM-CSF treated macrophages and negatively regulated by IL-10, dexamethasone and LPS. J. Immunol. 171: 4569-4573. Full Text

Willment JA, Marshall ASJ, Reid DM, et al. 2005. The human β-glucan receptor is widely expressed and functionally equivalent to murine Dectin-1 on primary cells. Eur. J. Immunol. 35: 1539-1547.


David W. Denning, MD

University of Manchester
Wythenshawe Hospital
e-mail | web site | publications

David Denning is professor of medicine and medical mycology at the University of Manchester, England, and an honorary consultant at Wythenshawe Hospital, also in Manchester. Denning's research interests include the treatment of invasive aspergillosis and the assessment of new antifungal agents. He has authored or coauthored more than 300 peer-reviewed journal articles and has coauthored an undergraduate textbook in medicine. He leads a 20-strong research group in Manchester.

Denning is a founder of the antifungal discovery and development company, F2G Ltd and the molecular diagnostic company Myconostica Ltd. He manages The Aspergillus Website. He also consults for the pharmaceutical industry with regard to antifungal drug development.

Denning earned his medical degree at Guy's Hospital, University of London, in 1980. He received clinical training in internal medicine and infectious diseases in Glasgow and London, including at the Medical Research Council (MRC) Clinical Research Center in London. He completed a fellowship in diagnostic microbiology and infectious diseases at the Santa Clara Valley Medical Center and Stanford University, California.

Kieren A. Marr, MD

Fred Hutchinson Cancer Research Center, University of Washington
e-mail | web site | publications

Kieran Marr is professor of medicine and director of transplant infectious diseases and the ID Clinical Research Center, Oregon Health and Sciences University. Before relocation to Portland, Oregon this year, she was an associate member in the Program of Infectious Diseases and associate professor in the Department of Medicine at the University of Washington, Seattle. She runs a laboratory that focuses on immunity to pathogenic fungi, and her clinical research focuses on algorithms to prevent infection in transplant recipients. She sits on numerous advisory boards, has published more than 100 per review articles on infection in transplant recipients, and is an editor of two text books in the field.

Thomas J. Walsh, MD

National Cancer Institute
e-mail | web site | publications

Thomas Walsh is a senior investigator and chief of the Immunocompromised Host Section in the Pediatric Oncology Branch of the National Cancer Institute. He obtained his MD from the Johns Hopkins University, and received additional postdoctoral training in pathology, pharmacology, immunology, and medical mycology. Boarded in infectious diseases and oncology, Walsh directs a combined laboratory and clinical translational research program dedicated to the molecular detection, immunomodulation, and pharmacotherapeutics of invasive fungal infections in children and adults with cancer and HIV infection.

Jean-Paul Latgé, PhD

Pasteur Institute
e-mail | web site | publications

Jean-Paul Latgé is professor at the Pasteur Institute in Paris and is the head of the Aspergillus Unit and the vice-chair of the Department of Parasitology and Mycology. The focus of the research of the Aspergillus Unit is on the biology of Aspergillus fumigatus and the study of Invasive Aspergillosis, now the most important mold infection worldwide. Expertise is mainly in the fields of fungal biochemistry, molecular biology, and immunology. Main achievements concern: (1) the chemical characterization of several antigens and development of the unique commercially available kit for the detection of invasive aspergillosis; (2) the analysis of the molecular epidemiology of invasive aspergillosis with its incidence on the prophylaxis of the disease; (3) the isolation and biochemical characterization of a dozen of proteins of A. fumigatus putatively involved in pathogenesis, cloning and disruption of the encoding genes and testing for pathogenicity in a murine model of pulmonary aspergillosis; (4) the study of the host-A. fumigatus interactions with special emphasis on the analysis of the innate and specific immunity and the identification of genes differentially expressed in vivo; (5) the structural analysis of the cell wall of hyphae and conidia of A. fumigatus and the characterization of synthases and glycosyltransferases involved in the cell wall assembly of A. fumigatus; (6) the development of large-scale biological studies, including comparative genomics, proteome and transcriptome analysis.

Gordon D. Brown, PhD

University of Cape Town, South Africa
e-mail | web site | publications

Gordon Brown was born in South Africa and completed a PhD in microbiology at the University of Cape Town. In 1999, after two years with the late Albert Beyers at the University of Stellenbosch, he moved to the Sir William Dunn School of Pathology at the University of Oxford, where he spent the next five years working with Siamon Gordon on pattern recognition receptors. In 2004, he moved back to the University of Cape Town as a Wellcome Trust Senior Research fellow. His primary research interests are macrophage receptors and their role in immunity.

Marilynn Larkin

Marilynn Larkin is a medical editor, journalist, and videographer based in New York City. Her work has frequently appeared in, among others, The Lancet, The Lancet Infectious Diseases, and Reuters Health's professional newswire. She is currently head of publications for The Society for Biomolecular Screening.

Ms. Larkin has served as editor of clinical publications for neurologists, anesthesiologists, HIV providers, and long-term care professionals. She also developed physician/patient education videos and continuing medical education symposia for several medical communications companies.

Prior to her work for physician audiences, she covered health, nutrition, fitness, psychology, and travel for women's and general interest magazines. She is also author of five medical books for general readers, and of Reporting on Health Risk, a handbook for journalists.

In 2004, Ms. Larkin started her own fitness consulting company (, and developed a class, Posture-cize, that helps people improve their posture, increase productivity, and reduce injury.