Cryptococcal Cell Morphology Affects Host Cell Interactions and Pathogenicity
Cryptococcus neoformans is a common life-threatening human fungal pathogen. The size of cryptococcal cells is typically 5 to 10 µm. Cell enlargement was observed in vivo, producing cells up to 100 µm. These morphological changes in cell size affected pathogenicity via reducing phagocytosis by host mononuclear cells, increasing resistance to oxidative and nitrosative stress, and correlated with reduced penetration of the central nervous system. Cell enlargement was stimulated by coinfection with strains of opposite mating type, and ste3aΔ pheromone receptor mutant strains had reduced cell enlargement. Finally, analysis of DNA content in this novel cell type revealed that these enlarged cells were polyploid, uninucleate, and produced daughter cells in vivo. These results describe a novel mechanism by which C. neoformans evades host phagocytosis to allow survival of a subset of the population at early stages of infection. Thus, morphological changes play unique and specialized roles during infection.
Vyšlo v časopise:
Cryptococcal Cell Morphology Affects Host Cell Interactions and Pathogenicity. PLoS Pathog 6(6): e32767. doi:10.1371/journal.ppat.1000953
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1000953
Souhrn
Cryptococcus neoformans is a common life-threatening human fungal pathogen. The size of cryptococcal cells is typically 5 to 10 µm. Cell enlargement was observed in vivo, producing cells up to 100 µm. These morphological changes in cell size affected pathogenicity via reducing phagocytosis by host mononuclear cells, increasing resistance to oxidative and nitrosative stress, and correlated with reduced penetration of the central nervous system. Cell enlargement was stimulated by coinfection with strains of opposite mating type, and ste3aΔ pheromone receptor mutant strains had reduced cell enlargement. Finally, analysis of DNA content in this novel cell type revealed that these enlarged cells were polyploid, uninucleate, and produced daughter cells in vivo. These results describe a novel mechanism by which C. neoformans evades host phagocytosis to allow survival of a subset of the population at early stages of infection. Thus, morphological changes play unique and specialized roles during infection.
Zdroje
1. KleinBS
TebbetsB
2007 Dimorphism and virulence in fungi. Curr Opin Microbiol 10 314 319
2. San-BlasG
TravassosLR
FriesBC
GoldmanDL
CasadevallA
2000 Fungal morphogenesis and virulence. Med Mycol 38 Suppl 1 79 86
3. MorrowCA
FraserJA
2009 Sexual reproduction and dimorphism in the pathogenic basidiomycetes. FEMS Yeast Res 9 161 177
4. HungCY
XueJ
ColeGT
2007 Virulence mechanisms of Coccidioides. Ann N Y Acad Sci 1111 225 235
5. MavorAL
ThewesS
HubeB
2005 Systemic fungal infections caused by Candida species: epidemiology, infection process and virulence attributes. Curr Drug Targets 6 863 874
6. LorenzMC
BenderJA
FinkGR
2004 Transcriptional response of Candida albicans upon internalization by macrophages. Eukaryot Cell 3 1076 1087
7. JayatilakeJA
SamaranayakeYH
SamaranayakeLP
2005 An ultrastructural and a cytochemical study of candidal invasion of reconstituted human oral epithelium. J Oral Pathol Med 34 240 246
8. MitchellTG
PerfectJR
1995 Cryptococcosis in the era of AIDS–100 years after the discovery of Cryptococcus neoformans. Clin Microbiol Rev 8 515 548
9. CurrieBP
CasadevallA
1994 Estimation of the prevalence of cryptococcal infection among patients infected with the human immunodeficiency virus in New York City. Clin Infect Dis 19 1029 1033
10. PerfectJR
CasadevallA
2002 Cryptococcosis. Infect Dis Clin North Am 16: 837-874, v- vi
11. CasadevallA
PerfectJR
1998 Cryptococcus neoformans. Washington, D.C. ASM Press viii, 541
12. ParkBJ
WannemuehlerKA
MarstonBJ
GovenderN
PappasPG
2009 Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS 23 525 530
13. HullCM
DavidsonRC
HeitmanJ
2002 Cell identity and sexual development in Cryptococcus neoformans are controlled by the mating-type-specific homeodomain protein Sxi1α. Genes Dev 16 3046 3060
14. LevitzSM
NongSH
SeetooKF
HarrisonTS
SpeizerRA
1999 Cryptococcus neoformans resides in an acidic phagolysosome of human macrophages. Infect Immun 67 885 890
15. ChangYC
StinsMF
McCafferyMJ
MillerGF
PareDR
2004 Cryptococcal yeast cells invade the central nervous system via transcellular penetration of the blood-brain barrier. Infect Immun 72 4985 4995
16. CharlierC
NielsenK
DaouS
BrigitteM
ChretienF
2009 Evidence of a role for monocytes in dissemination and brain invasion by Cryptococcus neoformans. Infect Immun 77 120 127
17. FeldmesserM
TuckerS
CasadevallA
2001 Intracellular parasitism of macrophages by Cryptococcus neoformans. Trends Microbiol 9 273 278
18. Del PoetaM
2004 Role of phagocytosis in the virulence of Cryptococcus neoformans. Eukaryot Cell 3 1067 1075
19. LubertoC
Martinez-MarinoB
TaraskiewiczD
BolanosB
ChitanoP
2003 Identification of App1 as a regulator of phagocytosis and virulence of Cryptococcus neoformans. J Clin Invest 112 1080 1094
20. SantangeloR
ZoellnerH
SorrellT
WilsonC
DonaldC
2004 Role of extracellular phospholipases and mononuclear phagocytes in dissemination of cryptococcosis in a murine model. Infect Immun 72 2229 2239
21. ChenSH
StinsMF
HuangSH
ChenYH
Kwon-ChungKJ
2003 Cryptococcus neoformans induces alterations in the cytoskeleton of human brain microvascular endothelial cells. J Med Microbiol 52 961 970
22. SheaJM
KechichianTB
LubertoC
Del PoetaM
2006 The cryptococcal enzyme inositol phosphosphingolipid-phospholipase C confers resistance to the antifungal effects of macrophages and promotes fungal dissemination to the central nervous system. Infect Immun 74 5977 5988
23. McClellandCM
ChangYC
VarmaA
Kwon-ChungKJ
2004 Uniqueness of the mating system in Cryptococcus neoformans. Trends Microbiol 12 208 212
24. NielsenK
HeitmanJ
2007 Sex and virulence of human pathogenic fungi. Adv Genet 57 143 173
25. DavidsonRC
NicholsCB
CoxGM
PerfectJR
HeitmanJ
2003 A MAP kinase cascade composed of cell type specific and non-specific elements controls mating and differentiation of the fungal pathogen Cryptococcus neoformans. Mol Microbiol 49 469 485
26. Kwon-ChungKJ
1976 Morphogenesis of Filobasidiella neoformans, the sexual state of Cryptococcus neoformans. Mycologia 68 821 833
27. NielsenK
CoxGM
WangP
ToffalettiDL
PerfectJR
2003 Sexual cycle of Cryptococcus neoformans var. grubii and virulence of congenic a and α isolates. Infect Immun 71 4831 4841
28. HullCM
BoilyMJ
HeitmanJ
2005 Sex-specific homeodomain proteins Sxi1α and Sxi2a coordinately regulate sexual development in Cryptococcus neoformans. Eukaryot Cell 4 526 535
29. FeldmesserM
KressY
CasadevallA
2001 Dynamic changes in the morphology of Cryptococcus neoformans during murine pulmonary infection. Microbiology 147 2355 2365
30. CruickshankJG
CavillR
JelbertM
1973 Cryptococcus neoformans of unusual morphology. Appl Microbiol 25 309 312
31. D'SouzaCA
AlspaughJA
YueC
HarashimaT
CoxGM
2001 Cyclic AMP-dependent protein kinase controls virulence of the fungal pathogen Cryptococcus neoformans. Mol Cell Biol 21 3179 3191
32. LoveGL
BoydGD
GreerDL
1985 Large Cryptococcus neoformans isolated from brain abscess. J Clin Microbiol 22 1068 1070
33. NielsenK
CoxGM
LitvintsevaAP
MylonakisE
MalliarisSD
2005 Cryptococcus neoformans α strains preferentially disseminate to the central nervous system during coinfection. Infect Immun 73 4922 4933
34. ChretienF
LortholaryO
KansauI
NeuvilleS
GrayF
2002 Pathogenesis of cerebral Cryptococcus neoformans infection after fungemia. J Infect Dis 186 522 530
35. CharlierC
ChretienF
BaudrimontM
MordeletE
LortholaryO
2005 Capsule structure changes associated with Cryptococcus neoformans crossing of the blood-brain barrier. Am J Pathol 166 421 432
36. JanewayC
MurphyKP
TraversP
WalportM
2008 Janeway's immunobiology. New York, NY Garland Science
37. BloomJ
CrossFR
2007 Multiple levels of cyclin specificity in cell-cycle control. Nat Rev Mol Cell Biol 8 149 160
38. HaroldFM
1990 To shape a cell: an inquiry into the causes of morphogenesis of microorganisms. Microbiol Rev 54 381 431
39. SloatBF
AdamsA
PringleJR
1981 Roles of the CDC24 gene product in cellular morphogenesis during the Saccharomyces cerevisiae cell cycle. J Cell Biol 89 395 405
40. OttoSP
2007 The evolutionary consequences of polyploidy. Cell 131 452 462
41. ZaragozaO
Carcia-RodasR
NosanchukJ
Cuenca-EstrellaM
Rodriguez-TudelaJL
CasadevallA
2010 Fungal cell giantism during mammalian infection. PLoS Pathog in press
42. WaughMS
NicholsCB
DeCesareCM
CoxGM
HeitmanJ
2002 Ras1 and Ras2 contribute shared and unique roles in physiology and virulence of Cryptococcus neoformans. Microbiology 148 191 201
43. GalitskiT
SaldanhaAJ
StylesCA
LanderES
FinkGR
1999 Ploidy regulation of gene expression. Science 285 251 254
44. AndalisAA
StorchovaZ
StylesC
GalitskiT
PellmanD
2004 Defects arising from whole-genome duplications in Saccharomyces cerevisiae. Genetics 167 1109 1121
45. StorchovaZ
BrenemanA
CandeJ
DunnJ
BurbankK
2006 Genome-wide genetic analysis of polyploidy in yeast. Nature 443 541 547
46. CushionMT
2004 Pneumocystis: unraveling the cloak of obscurity. Trends Microbiol 12 243 249
47. BeckJM
CushionMT
2009 Pneumocystis Workshop: 10th Anniversary Summary. Eukaryot Cell
48. ThomasCF
ParkJG
LimperAH
PuriV
2001 Analysis of a pheromone receptor and MAP kinase suggest a sexual replicative cycle in Pneumocystis carinii. J Eukaryot Microbiol Suppl 141S
49. SmulianAG
SesterhennT
TanakaR
CushionMT
2001 The ste3 pheromone receptor gene of Pneumocystis carinii is surrounded by a cluster of signal transduction genes. Genetics 157 991 1002
50. ThomasCFJr
LimperAH
2004 Pneumocystis pneumonia. N Engl J Med 350 2487 2498
51. HuppertM
SunSH
HarrisonJL
1982 Morphogenesis throughout saprobic and parasitic cycles of Coccidioides immitis. Mycopathologia 78 107 122
52. JohannessonH
KasugaT
SchallerRA
GoodB
GardnerMJ
2006 Phase-specific gene expression underlying morphological adaptations of the dimorphic human pathogenic fungus, Coccidioides posadasii. Fungal Genet Biol 43 545 559
53. LiL
SchmelzM
KellnerEM
GalgianiJN
OrbachMJ
2007 Nuclear labeling of Coccidioides posadasii with green fluorescent protein. Ann N Y Acad Sci 1111 198 207
54. IdnurmA
BahnYS
NielsenK
LinX
FraserJA
2005 Deciphering the model pathogenic fungus Cryptococcus neoformans. Nat Rev Microbiol 3 753 764
55. SteenbergenJN
CasadevallA
2003 The origin and maintenance of virulence for the human pathogenic fungus Cryptococcus neoformans. Microbes Infect 5 667 675
56. FanW
KrausPR
BoilyMJ
HeitmanJ
2005 Cryptococcus neoformans gene expression during murine macrophage infection. Eukaryot Cell 4 1420 1433
57. KrausPR
BoilyMJ
GilesSS
StajichJE
AllenA
2004 Identification of Cryptococcus neoformans temperature-regulated genes with a genomic-DNA microarray. Eukaryot Cell 3 1249 1260
58. GoldmanD
ChoY
ZhaoM
CasadevallA
LeeSC
1996 Expression of inducible nitric oxide synthase in rat pulmonary Cryptococcus neoformans granulomas. Am J Pathol 148 1275 1282
59. GoldmanD
LeeSC
CasadevallA
1994 Pathogenesis of pulmonary Cryptococcus neoformans infection in the rat. Infect Immun 62 4755 4761
60. GoldmanDL
DavisJ
BommaritoF
ShaoX
CasadevallA
2006 Enhanced allergic inflammation and airway responsiveness in rats with chronic Cryptococcus neoformans infection: potential role for fungal pulmonary infection in the pathogenesis of asthma. J Infect Dis 193 1178 1186
61. GoldmanDL
LeeSC
MednickAJ
MontellaL
CasadevallA
2000 Persistent Cryptococcus neoformans pulmonary infection in the rat is associated with intracellular parasitism, decreased inducible nitric oxide synthase expression, and altered antibody responsiveness to cryptococcal polysaccharide. Infect Immun 68 832 838
62. HeW
CasadevallA
LeeSC
GoldmanDL
2003 Phagocytic activity and monocyte chemotactic protein expression by pulmonary macrophages in persistent pulmonary cryptococcosis. Infect Immun 71 930 936
63. ShaoX
MednickA
AlvarezM
van RooijenN
CasadevallA
2005 An innate immune system cell is a major determinant of species-related susceptibility differences to fungal pneumonia. J Immunol 175 3244 3251
64. ShaoX
RiveraJ
NiangR
CasadevallA
GoldmanDL
2005 A dual role for TGF-β1 in the control and persistence of fungal pneumonia. J Immunol 175 6757 6763
65. Garcia-HermosoD
JanbonG
DromerF
1999 Epidemiological evidence for dormant Cryptococcus neoformans infection. J Clin Microbiol 37 3204 3209
66. DromerF
AucouturierP
ClauvelJP
SaimotG
YeniP
1988 Cryptococcus neoformans antibody levels in patients with AIDS. Scand J Infect Dis 20 283 285
67. DubeyJP
2004 Toxoplasmosis - a waterborne zoonosis. Vet Parasitol 126 57 72
68. BladerIJ
SaeijJP
2009 Communication between Toxoplasma gondii and its host: impact on parasite growth, development, immune evasion, and virulence. APMIS 117 458 476
69. JusticeSS
HunstadDA
CegelskiL
HultgrenSJ
2008 Morphological plasticity as a bacterial survival strategy. Nat Rev Microbiol 6 162 168
70. GoldenJW
LinkeJ
SchmechelS
ThoemkeK
SchiffLA
2002 Addition of exogenous protease facilitates reovirus infection in many restrictive cells. J Virol 76 7430 7443
71. ChandranK
NibertML
2003 Animal cell invasion by a large nonenveloped virus: reovirus delivers the goods. Trends Microbiol 11 374 382
72. NibertML
FurlongDB
FieldsBN
1991 Mechanisms of viral pathogenesis. Distinct forms of reoviruses and their roles during replication in cells and host. J Clin Invest 88 727 734
73. FraserJA
SubaranRL
NicholsCB
HeitmanJ
2003 Recapitulation of the sexual cycle of the primary fungal pathogen Cryptococcus neoformans var. gattii: implications for an outbreak on Vancouver Island, Canada. Eukaryot Cell 2 1036 1045
74. HsuehYP
FraserJA
HeitmanJ
2008 Transitions in sexuality: recapitulation of an ancestral tri- and tetrapolar mating system in Cryptococcus neoformans. Eukaryot Cell 7 1847 1855
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