The temporal dynamics of differential gene expression in Aspergillus fumigatus interacting with human immature dendritic cells in vitro.
Dendritic cells (DC) are the most important antigen presenting cells and play a pivotal role in host immunity to infectious agents by acting as a bridge between the innate and adaptive immune systems. Monocyte-derived immature DCs (iDC) were infected with viable resting conidia of Aspergillus fumigatus (Af293) for 12 hours at an MOI of 5; cells were sampled every three hours. RNA was extracted from both organisms at each time point and hybridised to microarrays. iDC cell death increased at 6 h in the presence of A. fumigatus which coincided with fungal germ tube emergence; >80% of conidia were associated with iDC. Over the time course A. fumigatus differentially regulated 210 genes, FunCat analysis indicated significant up-regulation of genes involved in fermentation, drug transport, pathogenesis and response to oxidative stress. Genes related to cytotoxicity were differentially regulated but the gliotoxin biosynthesis genes were down regulated over the time course, while Aspf1 was up-regulated at 9 h and 12 h. There was an up-regulation of genes in the subtelomeric regions of the genome as the interaction progressed. The genes up-regulated by iDC in the presence of A. fumigatus indicated that they were producing a pro-inflammatory response which was consistent with previous transcriptome studies of iDC interacting with A. fumigatus germ tubes. This study shows that A. fumigatus adapts to phagocytosis by iDCs by utilising genes that allow it to survive the interaction rather than just up-regulation of specific virulence genes.
Department of Clinical Microbiology, Trinity College Dublin, Dublin, Ireland.
Charles O
CO
Morton
John J
JJ
Varga
Anke
A
Hornbach
Markus
M
Mezger
Helga
H
Sennefelder
Susanne
S
Kneitz
Oliver
O
Kurzai
Sven
S
Krappmann
Hermann
H
Einsele
William C
WC
Nierman
Thomas R
TR
Rogers
Juergen
J
Loeffler
D001232:Aspergillus fumigatus / Q000235:genetics*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000382:microbiology*; D005786:Gene Expression Regulation / Q000276:immunology*; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D057131:Immune Evasion / Q000235:genetics; D007249:Inflammation / Q000235:genetics; D010587:Phagocytosis
Trends Microbiol. 2008 Jan;16(1):27-32
18160296
BMC Genomics. 2008 Sep 16;9:417
18796135
Med Mycol. 2009;47 Suppl 1:S72-9
19253141
Bioinformatics. 2002;18 Suppl 1:S96-104
12169536
Microbes Infect. 2009 Oct;11(12):919-27
19615460
Methods. 2003 Dec;31(4):265-73
14597310
Appl Environ Microbiol. 2009 Jan;75(2):493-503
19028908
Nature. 2009 Aug 27;460(7259):1117-21
19713928
Nucleic Acids Res. 2007 Jul;35(Web Server issue):W71-4
17485472
Cell Physiol Biochem. 2008;21(1-3):215-24
18209488
J Proteome Res. 2010 Jul 2;9(7):3427-42
20507060
Nature. 2009 Jan 22;457(7228):471-4
19043401
Nucleic Acids Res. 2004 Oct 14;32(18):5539-45
15486203
Infect Immun. 2001 Oct;69(10):6411-8
11553585
Bioinformatics. 2005 May 1;21(9):2067-75
15657102
Int Immunol. 2009 Nov;21(11):1251-62
19736294
Infect Immun. 2003 Jun;71(6):3551-62
12761140
PLoS Pathog. 2005 Dec;1(4):e42
16344862
PLoS Pathog. 2008 Sep 12;4(9):e1000154
18787699
Front Biosci. 2003 May 01;8:s346-57
12700046
Infect Immun. 2006 Apr;74(4):2353-65
16552065
J Infect Dis. 2008 Mar 15;197(6):924-31
18279049
Med Mycol. 2009;47 Suppl 1:S291-8
19306226
Cell. 2006 Jul 14;126(1):17-9
16839868
Cytokine Growth Factor Rev. 2007 Feb-Apr;18(1-2):5-17
17321783
Clin Infect Dis. 2009 Feb 1;48(3):265-73
19115967
FEMS Microbiol Rev. 2007 Mar;31(2):212-37
17253975
J Immunol. 2002 Feb 1;168(3):1362-71
11801677
Blood. 2008 Jan 15;111(2):534-6
17957030
Mol Microbiol. 2004 May;52(3):785-99
15101984
Biotechniques. 2003 Feb;34(2):374-8
12613259
Med Mycol. 2005 May;43 Suppl 1:S95-9
16110799
Infect Immun. 2001 Apr;69(4):2402-6
11254600
Trends Microbiol. 2002 Nov;10(11):508-14
12419615
Curr Biol. 2004 Nov 23;14(22):R965-7
15556856
J Immunol. 2004 Nov 1;173(9):5635-43
15494514
Nature. 2005 Dec 22;438(7071):1151-6
16372009
Fungal Genet Biol. 2009 Dec;46(12):909-18
19715768
Med Mycol. 2008 Sep;46(6):515-29
19180748
Genome Biol. 2004;5(10):R80
15461798
Cell Microbiol. 2007 Jun;9(6):1588-600
17371405
J Cell Biol. 2006 Aug 14;174(4):509-19
16893972
Planta Med. 2006 Oct;72(12):1117-20
16902860
Curr Opin Immunol. 2002 Aug;14(4):420-31
12088675
Mol Microbiol. 2000 Jun;36(6):1371-80
10931287
Eukaryot Cell. 2009 Jan;8(1):104-15
19028996
BMC Microbiol. 2009 Aug 24;9:177
19703288
Med Mycol. 2009;47 Suppl 1:S97-103
18608908
Blood. 2005 Mar 15;105(6):2258-65
15546954
Immunobiology. 2005;210(2-4):175-83
16164024
Fungal Genet Biol. 2009 Mar;46 Suppl 1:S105-20
18703157
Infect Immun. 2006 Mar;74(3):1480-9
16495518
Genome Biol. 2003;4(10):R70
14519205
Clin Vaccine Immunol. 2009 Oct;16(10):1485-92
19675222
PLoS Pathog. 2007 Sep 28;3(9):1195-207
17845073
Med Mycol. 2007 Mar;45(2):123-30
17365648
Cell. 2006 Jul 14;126(1):205-18
16839887
Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5116-21
11309499
Nihon Ishinkin Gakkai Zasshi. 2006;47(4):249-55
17086155
Nat Protoc. 2008;3(7):1125-31
18600217
Fungal Genet Biol. 2008 Jul;45(7):1135-46
18538268
Clin Microbiol Rev. 1999 Apr;12(2):310-50
10194462
J Med Microbiol. 2009 Jan;58(Pt 1):49-58
19074652
Mol Microbiol. 2010 Feb;75(4):910-23
20487287
PLoS One. 2008 Jul 09;3(7):e2655
18648542
Science. 2001 Oct 26;294(5543):870-5
11679675
Clin Immunol. 2007 Sep;124(3):238-43
17604224
Clin Microbiol Rev. 2009 Jul;22(3):447-65
19597008
Trends Microbiol. 2008 Jun;16(6):291-300
18457952
Mucosal Immunol. 2010 Mar;3(2):193-205
19924119
Med Mycol. 2006 Sep 1;44(Supplement_1):S219-S227
30408907
Fungal Genet Biol. 2008 May;45(5):693-704
18249572
Toxicon. 1999 Nov;37(11):1549-63
10482390
Annu Rev Immunol. 1996;14:649-83
8717528
Cell Microbiol. 2008 Jan;10(1):134-48
17973657
Curr Opin Microbiol. 2005 Aug;8(4):385-92
16019255
Med Mycol. 2010 Feb;48(1):1-15
19462332
Med Mycol. 2005 May;43 Suppl 1:S173-6
16110808
Curr Opin Microbiol. 2008 Aug;11(4):331-7
18579432
Med Mycol. 2006 Sep 1;44(Supplement_1):S91-S94
30408941