Georgios Chamilos
Airborne filamentous fungi (molds) are ubiquitous, saprophytic organisms that constantly interact with the immune system without causing disease in healthy individuals. These opportunistic pathogens are emerging causes of life-threatening respiratory infections in an expanding population of immunocompromised patients. Our group is interested to explore (a) host and pathogen molecular determinants of the intracellular fate of fungi inside phagocytes, and (b) mechanisms of immunodeficiency that drive the development of fungal diseases. In order to dissect the complexity of host-fungal interplay we utilize genetic approaches in murine and human primary immune cells, cell lines, and animal models of fungal diseases in transgenic mice.
Kyrmizi I, Ferreira H, Carvalho A, Landero Figueroa JA, Zarmpas P, Cunha C, Akoumianaki T, Deepe, Jr GS, Samonis G, Lacerda JF, Campos Jr AC, Kontoyiannis DP, Mihalopoulos N, Valsecchi I, Beauvais A, Brakhage AA, Neves NM, Latge JP, Chamilos G. (2018) Calcium sequestration by fungal melanin inhibits calcium-calmodulin signalling to prevent LC3-associated phagocytosis. Nat Microbiol. 3:791-803.
Andrianaki A, Kyrmizi I, Panopoulou K, Baldin K, Drakos E, Soliman SSM, Akoumianaki T, Stylianou K, Ioannou P, Belle V, Emilien E, Beauvais A, Samonis G, Kontoyiannis DP, Andreakos E, Bruno V, Ibrahim AS, Chamilos G (2018) Iron restriction inside macrophages regulates pulmonary host defense against Rhizopus species. Nat Commun. 9:3333.
Akoumianaki T, Kyrmizi I, Valsecchi I, Gresnigt MS, Samonis G, Drakos E, Boumpas D, Muszkieta L, Prevost MC, Kontoyiannis DP, Chavakis T, Netea MG, van de Veerdonk FL, Brakhage AA, El-Benna J, Beauvais A, Latge JP, Chamilos G. (2016) Aspergillus Cell Wall Melanin Blocks LC3-Associated Phagocytosis to Promote Pathogenicity. Cell Host Microbe 19:79-90.
Kyrmizi I, Gresnigt MS, Akoumianaki T, Samonis G, Sidiropoulos P, Boumpas D, Netea MG, van de Veerdonk FL, Kontoyiannis DP, Chamilos G (2013) Corticosteroids Block Autophagy Protein Recruitment in Aspergillus fumigatus Phagosomes via Targeting Dectin-1/Syk Kinase Signaling. J Immunol. 191:1287-99.
Chamilos G, Gregorio J, Meller S, Lande R, Kontoyiannis DP, Modlin RL, Gilliet M. (2012) Cytosolic sensing of extracellular self-DNA transported into monocytes by the antimicrobial peptide LL37. Blood 120:3699-707.
Latgé JP, Beauvais A, Chamilos G. The Cell Wall of the Human Fungal PathogenAspergillus fumigatus: Biosynthesis, Organization, Immune Response, and Virulence. Annu Rev Microbiol. 2017 Sep 8;71:99-116. (Review)
Chamilos G, Lionakis MS, Kontoyiannis DP. Call for Action: Invasive Fungal Infections Associated With Ibrutinib and Other Small Molecule Kinase Inhibitors Targeting Immune Signaling Pathways. Clin Infect Dis. 2018 Jan 6;66(1):140-148. (Viewpoint, Review article)
Akoumianaki T, Chamilos G. DAPK1 Keeps the Peace in Antifungal Inflammation. Cell Host Microbe. 2016 Dec 14;20(6):695-697. (Commentary)
Ioannou P, Andrianaki A, Akoumianaki T, Kyrmizi I, Albert N, Perlin D, Samonis G, Kontoyiannis DP, Chamilos G. Albumin Enhances Caspofungin Activity against Aspergillus Species by Facilitating Drug Delivery to Germinating Hyphae. Antimicrob Agents Chemother. 2015 Dec 7;60(3):1226-33.
Meller S, Di Domizio J, Voo KS, Friedrich HC, Chamilos G, Ganguly D, Conrad C, Gregorio J, Le Roy D, Roger T, Ladbury JE, Homey B, Watowich S, Modlin RL, Kontoyiannis DP, Liu YJ, Arold ST, Gilliet M. T(H)17 cells promote microbial killing and innate immune sensing of DNA via interleukin 26. Nat Immunol. 2015 Sep;16(9):970-9.
Lande R, Botti E, Jandus C, Dojcinovic D, Fanelli G, Conrad C, Chamilos G, Feldmeyer L, Marinari B, Chon S, Vence L, Riccieri V, Guillaume P, Navarini AA, Romero P, Costanzo A, Piccolella E, Gilliet M, Frasca L. The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis. Nat Commun. 2014 Dec 3;5:5621.
Buffen K, Oosting M, Quintin J, Ng A, Kleinnijenhuis J, Kumar V, van de Vosse E, Wijmenga C, van Crevel R, Oosterwijk E, Grotenhuis AJ, Vermeulen SH, Kiemeney LA, van de Veerdonk FL, Chamilos G, Xavier RJ, van der Meer JW, Netea MG, Joosten LA. Autophagy controls BCG-induced trained immunity and the response to intravesical BCG therapy for bladder cancer. PLoS Pathog. 2014 Oct 30;10(10):e1004485.
Lande R*, Chamilos G*, Ganguly D*, Demaria O, Frasca L, Durr S, Conrad C, Schröder J, Gilliet M. Cationic antimicrobial peptides in psoriatic skin cooperate to break innate tolerance to self-DNA. Eur J Immunol. 2015 Jan;45(1):203-13. * Equal contribution
de Luca A, Smeekens SP, Casagrande A, Iannitti R, Conway KL, Gresnigt MS, Begun J, Plantinga TS, Joosten LA, van der Meer JW, Chamilos G, Netea MG, Xavier RJ, Dinarello CA, Romani L, van de Veerdonk FL. IL-1 receptor blockade restores autophagy and reduces inflammation in chronic granulomatous disease in mice and in humans. Proc Natl Acad Sci U S A. 2014 Mar 4;111(9):3526-31.
Lande R, Ganguly D, Facchinetti V, Frasca L, Conrad C, Gregorio J, Meller S, Chamilos G, Sebasigari R, Riccieri V, Bassett R, Amuro H, Fukuhara S, Ito T, Liu YJ, Gilliet M. Neutrophils activate plasmacytoid dendritic cells by releasing self-DNA-peptide complexes in systemic lupus erythematosus. Sci Transl Med. 2011 Mar 9;3(73):73ra19.
Chamilos G, Ganguly D, Lande R, Gregorio J, Meller S, Goldman WE, Gilliet M, Kontoyiannis DP. Generation of IL-23 producing dendritic cells (DCs) by airborne fungi regulates fungal pathogenicity via the induction of T(H)-17 responses. PLoS One. 2010 Sep 23;5(9):e12955.
Chamilos G, Bignell EM, Schrettl M, Lewis RE, Leventakos K, May GS, Haas H, Kontoyiannis DP. Exploring the concordance of Aspergillus fumigatus pathogenicity in mice and Toll-deficient flies. Med Mycol. 2010 May;48(3):506-10.
Ganguly D, Chamilos G, Lande R, Gregorio J, Meller S, Facchinetti V, Homey B, Barrat FJ, Zal T, Gilliet M. Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8. J Exp Med. 2009 Aug31;206(9):1983-94.
Chamilos G, Nobile CJ, Bruno VM, Lewis RE, Mitchell AP, Kontoyiannis DP. Candida albicans Cas5, a regulator of cell wall integrity, is required for virulence in murine and toll mutant fly models. J Infect Dis. 2009 Jul 1;200(1):152-7.
Chamilos G, Lewis RE, Hu J, Xiao L, Zal T, Gilliet M, Halder G, Kontoyiannis DP. Drosophila melanogaster as a model host to dissect the immunopathogenesis of zygomycosis. Proc Natl Acad Sci U S A. 2008 Jul 8;105(27):9367-72.
Chamilos G, Lewis RE, Lamaris GA, Albert ND, Kontoyiannis DP. Genomewide screening for genes associated with gliotoxin resistance and sensitivity in Saccharomyces cerevisiae. Antimicrob Agents Chemother. 2008 Apr;52(4):1325-9.
Chamilos G, Lewis RE, Lamaris G, Walsh TJ, Kontoyiannis DP. Zygomycetes hyphae trigger an early, robust proinflammatory response in human polymorphonuclear neutrophils through toll-like receptor 2 induction but display relative resistance to oxidative damage. Antimicrob Agents Chemother. 2008 Feb;52(2):722-4.
Lewis RE, Chamilos G, Prince RA, Kontoyiannis DP. Pretreatment with empty liposomes attenuates the immunopathology of invasive pulmonary aspergillosis in corticosteroid-immunosuppressed mice. Antimicrob Agents Chemother. 2007 Mar;51(3):1078-81.
Chamilos G, Lionakis MS, Lewis RE, Lopez-Ribot JL, Saville SP, Albert ND, Halder G, Kontoyiannis DP. Drosophila melanogaster as a facile model for large-scale studies of virulence mechanisms and antifungal drug efficacy in Candida species. J Infect Dis. 2006 Apr 1;193(7):1014-22.
Chamilos G, Lewis RE, Kontoyiannis DP. Inhibition of Candida parapsilosis mitochondrial respiratory pathways enhances susceptibility to caspofungin. Antimicrob Agents Chemother. 2006 Feb;50(2):744-7.
Lionakis MS*, Chamilos G*, Lewis RE, Wiederhold NP, Raad II, Samonis G, Kontoyiannis DP. Pentamidine is active in a neutropenic murine model of acute invasive pulmonary fusariosis. Antimicrob Agents Chemother. 2006 Jan;50(1):294-7. * Equal contribution
Chamilos G, Lewis RE, Kontoyiannis DP. Lovastatin has significant activity against zygomycetes and interacts synergistically with voriconazole. Antimicrob Agents Chemother. 2006 Jan;50(1):96-103.