#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Fungal Cell Gigantism during Mammalian Infection


The interaction between fungal pathogens with the host frequently results in morphological changes, such as hyphae formation. The encapsulated pathogenic fungus Cryptococcus neoformans is not considered a dimorphic fungus, and is predominantly found in host tissues as round yeast cells. However, there is a specific morphological change associated with cryptococcal infection that involves an increase in capsule volume. We now report another morphological change whereby gigantic cells are formed in tissue. The paper reports the phenotypic characterization of giant cells isolated from infected mice and the cellular changes associated with giant cell formation. C. neoformans infection in mice resulted in the appearance of giant cells with cell bodies up to 30 µm in diameter and capsules resistant to stripping with γ-radiation and organic solvents. The proportion of giant cells ranged from 10 to 80% of the total lung fungal burden, depending on infection time, individual mice, and correlated with the type of immune response. When placed on agar, giant cells budded to produce small daughter cells that traversed the capsule of the mother cell at the speed of 20–50 m/h. Giant cells with dimensions that approximated those in vivo were observed in vitro after prolonged culture in minimal media, and were the oldest in the culture, suggesting that giant cell formation is an aging-dependent phenomenon. Giant cells recovered from mice displayed polyploidy, suggesting a mechanism by which gigantism results from cell cycle progression without cell fission. Giant cell formation was dependent on cAMP, but not on Ras1. Real-time imaging showed that giant cells were engaged, but not engulfed by phagocytic cells. We describe a remarkable new strategy for C. neoformans to evade the immune response by enlarging cell size, and suggest that gigantism results from replication without fission, a phenomenon that may also occur with other fungal pathogens.


Vyšlo v časopise: Fungal Cell Gigantism during Mammalian Infection. PLoS Pathog 6(6): e32767. doi:10.1371/journal.ppat.1000945
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1000945

Souhrn

The interaction between fungal pathogens with the host frequently results in morphological changes, such as hyphae formation. The encapsulated pathogenic fungus Cryptococcus neoformans is not considered a dimorphic fungus, and is predominantly found in host tissues as round yeast cells. However, there is a specific morphological change associated with cryptococcal infection that involves an increase in capsule volume. We now report another morphological change whereby gigantic cells are formed in tissue. The paper reports the phenotypic characterization of giant cells isolated from infected mice and the cellular changes associated with giant cell formation. C. neoformans infection in mice resulted in the appearance of giant cells with cell bodies up to 30 µm in diameter and capsules resistant to stripping with γ-radiation and organic solvents. The proportion of giant cells ranged from 10 to 80% of the total lung fungal burden, depending on infection time, individual mice, and correlated with the type of immune response. When placed on agar, giant cells budded to produce small daughter cells that traversed the capsule of the mother cell at the speed of 20–50 m/h. Giant cells with dimensions that approximated those in vivo were observed in vitro after prolonged culture in minimal media, and were the oldest in the culture, suggesting that giant cell formation is an aging-dependent phenomenon. Giant cells recovered from mice displayed polyploidy, suggesting a mechanism by which gigantism results from cell cycle progression without cell fission. Giant cell formation was dependent on cAMP, but not on Ras1. Real-time imaging showed that giant cells were engaged, but not engulfed by phagocytic cells. We describe a remarkable new strategy for C. neoformans to evade the immune response by enlarging cell size, and suggest that gigantism results from replication without fission, a phenomenon that may also occur with other fungal pathogens.


Zdroje

1. CasadevallA

PirofskiLA

2003 The damage-response framework of microbial pathogenesis. Nat Rev Microbiol 1 17 24

2. WhitewayM

BachewichC

2007 Morphogenesis in Candida albicans. Annu Rev Microbiol 61 529 553

3. SudberyP

GowN

BermanJ

2004 The distinct morphogenic states of Candida albicans. Trends Microbiol 12 317 324

4. LiuH

2001 Transcriptional control of dimorphism in Candida albicans. Curr Opin Microbiol 4 728 735

5. MarescaB

KobayashiGS

1989 Dimorphism in Histoplasma capsulatum: a model for the study of cell differentiation in pathogenic fungi. Microbiol Rev 53 186 209

6. KaneJ

1984 Conversion of Blastomyces dermatitidis to the yeast form at 37 degrees C and 26 degrees C. J Clin Microbiol 20 594 596

7. MarescaB

KobayashiGS

2000 Dimorphism in Histoplasma capsulatum and Blastomyces dermatitidis. Contrib Microbiol 5 201 216

8. ParkBI

WannemuehlerKA

MarstonBJ

GovenderN

PappasPG

2009 Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS 23 525 530

9. CasadevallA

PerfectJR

1998 Cryptococcus neoformans;

PressA

Washington DC ASM Press

10. CherniakR

1988 Soluble polysaccharides of Cryptococcus neoformans. Curr Top Med Mycol 2 40 54

11. GoldmanDL

LeeSC

CasadevallA

1995 Tissue localization of Cryptococcus neoformans glucuronoxylomannan in the presence and absence of specific antibody. Infect Immun 63 3448 3453

12. LeeSC

CasadevallA

DicksonDW

1996 Immunohistochemical localization of capsular polysaccharide antigen in the central nervous system cells in cryptococcal meningoencephalitis. Am J Pathol 148 1267 1274

13. VecchiarelliA

2007 Fungal capsular polysaccharide and T-cell suppression: the hidden nature of poor immunogenicity. Crit Rev Immunol 27 547 557

14. YauchLE

LamJS

LevitzSM

2006 Direct inhibition of T-cell responses by the Cryptococcus capsular polysaccharide glucuronoxylomannan. PLoS Pathog 2 e120

15. ZaragozaO

RodriguesML

De JesusM

FrasesS

DadachovaE

2009 The Capsule of the Fungal Pathogen Cryptococcus neoformans. Adv Appl Microbiol 68 133 216

16. McClellandEE

BernhardtP

CasadevallA

2006 Estimating the relative contributions of virulence factors for pathogenic microbes. Infect Immun 74 1500 1504

17. ZaragozaO

CasadevallA

2004 Experimental modulation of capsule size in Cryptococcus neoformans. Biol Proced Online 6 10 15

18. FeldmesserM

KressY

CasadevallA

2001 Dynamic changes in the morphology of Cryptococcus neoformans during murine pulmonary infection. Microbiology 147 2355 2365

19. MaxsonME

CookE

CasadevallA

ZaragozaO

2007 The volume and hydration of the Cryptococcus neoformans polysaccharide capsule. Fungal Genet Biol 44 180 186

20. ZaragozaO

TabordaCP

CasadevallA

2003 The efficacy of complement-mediated phagocytosis of Cryptococcus neoformans is dependent on the location of C3 in the polysaccharide capsule and involves both direct and indirect C3-mediated interactions. Euro J Immnunol 33 1957 1967

21. ZaragozaO

ChrismanCJ

CastelliMV

FrasesS

Cuenca-EstrellaM

2008 Capsule enlargement in Cryptococcus neoformans confers resistance to oxidative stress suggesting a mechanism for intracellular survival. Cell Microbiol 10 2043 2057

22. CruickshankJG

CavillR

JelbertM

1973 Cryptococcus neoformans of unusual morphology. Appl Microbiol 25 309 312

23. 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

24. LoveGL

BoydGD

GreerDL

1985 Large Cryptococcus neoformans isolated from brain abscess. J Clin Microbiol 22 1068 1070

25. ZaragozaO

MihuC

CasadevallA

NosanchukJD

2005 Effect of amphotericin B on capsule and cell size in Cryptococcus neoformans during murine infection. Antimicrob Agents Chemother 49 4358 4361

26. NosanchukJD

ValadonP

FeldmesserM

CasadevallA

1999 Melanization of Cryptococcus neoformans in murine infection. Mol Cell Biol 19 745 750

27. RosasAL

NosanchukJD

FeldmesserM

CoxGM

McDadeHC

2000 Synthesis of polymerized melanin by Cryptococcus neoformans in infected rodents. Infect Immun 68 2845 2853

28. ChaskesS

FrasesS

CammerM

GerfenG

CasadevallA

2008 Growth and pigment production on D-tryptophan medium by Cryptococcus gattii, Cryptococcus neoformans, and Candida albicans. J Clin Microbiol 46 255 264

29. BryanRA

ZaragozaO

ZhangT

OrtizG

CasadevallA

2005 Radiological studies reveal radial differences in the architecture of the polysaccharide capsule of Cryptococcus neoformans. Eukaryot Cell 4 465 475

30. DembitzerHM

BuzaI

ReissF

1972 Biological and electron microscopic changes in gamma radiated Cryptococcus neoformans. Mycopathol Mycol Appl 47 307 315

31. GatesMA

ThorkildsonP

KozelTR

2004 Molecular architecture of the Cryptococcus neoformans capsule. Mol Microbiol 52 13 24

32. ZaragozaO

CasadevallA

2006 Monoclonal antibodies can affect complement deposition on the capsule of the pathogenic fungus Cryptococcus neoformans by both classical pathway activation and steric hindrance. Cell Microbiol 8 1862 1876

33. RodriguesML

AlvarezM

FonsecaFL

CasadevallA

2008 Binding of the wheat germ lectin to Cryptococcus neoformans suggests an association of chitinlike structures with yeast budding and capsular glucuronoxylomannan. Eukaryot Cell 7 602 609

34. ZaragozaO

TelzakA

BryanRA

DadachovaE

CasadevallA

2006 The polysaccharide capsule of the pathogenic fungus Cryptococcus neoformans enlarges by distal growth and is rearranged during budding. Mol Microbiol 59 67 83

35. MiyajiM

NishimuraK

AjelloL

1985 Scanning electron microscope studies on the parasitic cycle of Coccidioides immitis. Mycopathologia 89 51 57

36. de HoogGS

GuarroJ

GenéJ

FiguerasMJ

2000 Atlas of Clinical Fungi;

de HoogGS

GuarroJ

GenéJ

FiguerasMJ

Utrecht, Reus Centraalbureau vor Schimmel Cultures, Universitat Rovira i Virgili

37. AlspaughJA

Pukkila-WorleyR

HarashimaT

CavalloLM

FunnellD

2002 Adenylyl cyclase functions downstream of the Galpha protein Gpa1 and controls mating and pathogenicity of Cryptococcus neoformans. Eukaryot Cell 1 75 84

38. AlspaughJA

CavalloLM

PerfectJR

HeitmanJ

2000 RAS1 regulates filamentation, mating and growth at high temperature of Cryptococcus neoformans. Mol Microbiol 36 352 365

39. AlvarezM

CasadevallA

2006 Phagosome extrusion and host-cell survival after Cryptococcus neoformans phagocytosis by macrophages. Curr Biol 16 2161 2165

40. AlvarezM

CasadevallA

2007 Cell-to-cell spread and massive vacuole formation after Cryptococcus neoformans infection of murine macrophages. BMC Immunol 8 16

41. MaH

CroudaceJE

LammasDA

MayRC

2007 Direct cell-to-cell spread of a pathogenic yeast. BMC Immunol 8 15

42. MaH

CroudaceJE

LammasDA

MayRC

2006 Expulsion of live pathogenic yeast by macrophages. Curr Biol 16 2156 2160

43. LuoY

AlvarezM

XiaL

CasadevallA

2008 The outcome of phagocytic cell division with infectious cargo depends on single phagosome formation. PLoS One 3 e3219

44. CleareW

CasadevallA

1999 Scanning electron microscopy of encapsulated and non-encapsulated Cryptococcus neoformans and the effect of glucose on capsular polysaccharide release. Med Mycol 37 235 243

45. AldeaM

GariE

ColominaN

2007 Control of cell cycle and cell growth by molecular chaperones. Cell Cycle 6 2599 2603

46. Sugimoto-ShirasuK

RobertsK

2003 “Big it up”: endoreduplication and cell-size control in plants. Curr Opin Plant Biol 6 544 553

47. GrebienF

DolznigH

BeugH

MullnerEW

2005 Cell size control: new evidence for a general mechanism. Cell Cycle 4 418 421

48. Cavalier-SmithT

1978 Nuclear volume control by nucleoskeletal DNA, selection for cell volume and cell growth rate, and the solution of the DNA C-value paradox. J Cell Sci 34 247 278

49. KondorosiE

RoudierF

GendreauE

2000 Plant cell-size control: growing by ploidy? Curr Opin Plant Biol 3 488 492

50. MendellJE

ClementsKD

ChoatJH

AngertER

2008 Extreme polyploidy in a large bacterium. Proc Natl Acad Sci U S A 105 6730 6734

51. MergaertP

UchiumiT

AlunniB

EvannoG

CheronA

2006 Eukaryotic control on bacterial cell cycle and differentiation in the Rhizobium-legume symbiosis. Proc Natl Acad Sci U S A 103 5230 5235

52. 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

53. MoyrandF

FontaineT

JanbonG

2007 Systematic capsule gene disruption reveals the central role of galactose metabolism on Cryptococcus neoformans virulence. Mol Microbiol 64 771 781

54. CharlierC

NielsenK

DaouS

BrigitteM

ChretienF

2009 Evidence For A Role Of Monocytes In Dissemination And Brain Invasion By Cryptococcus Neoformans. Infect Immun 77 120 127

55. KechichianTB

SheaJ

Del PoetaM

2007 Depletion of alveolar macrophages decreases the dissemination of a glucosylceramide-deficient mutant of Cryptococcus neoformans in immunodeficient mice. Infect Immun 75 4792 4798

56. 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

57. ZaragozaO

AlvarezM

TelzakA

RiveraJ

CasadevallA

2007 The relative susceptibility of mouse strains to pulmonary Cryptococcus neoformans infection is associated with pleiotropic differences in the immune response. Infect Immun 75 2729 2739

58. NosanchukJD

RosasAL

LeeSC

CasadevallA

2000 Melanisation of Cryptococcus neoformans in human brain tissue. Lancet 355 2049 2050

59. BottoneEJ

HorgaM

AbramsJ

1999 “Giant” blastoconidia of Candida albicans: morphologic presentation and concepts regarding their production. Diagn Microbiol Infect Dis 34 27 32

60. AlasioTM

LentoPA

BottoneEJ

2003 Giant blastoconidia of Candida albicans. A case report and review of the literature. Arch Pathol Lab Med 127 868 871

61. PerfectJR

LangSDR

DurackDT

1980 Chronic cryptococcal meningitis: a new experimental model in rabbits. Am J Pathol 101 177 194

62. Kwon-ChungKJ

1976 Morphogenesis of Filobasidiella neoformans, the sexual state of Cryptococcus neoformans. Mycologia 68 821 833

63. Garcia-RiveraJ

EisenmanHC

NosanchukJD

AisenP

ZaragozaO

2005 Comparative analysis of Cryptococcus neoformans acid-resistant particles generated from pigmented cells grown in different laccase substrates. Fungal Genet Biol 42 989 998

64. FeldmesserM

KressY

NovikoffP

CasadevallA

2000 Cryptococcus neoformans is a facultative intracellular pathogen in murine pulmonary infection. Infect Immun 68 4225 4237

65. Glatman-FreedmanA

MartinJM

RiskaPF

BloomBR

CasadevallA

1996 Monoclonal antibodies to surface antigens of Mycobacterium tuberculosis and their use in a modified enzyme-linked immunosorbent spot assay for detection of mycobacteria. J Clin Microbiol 34 2795 2802

66. MaxsonME

DadachovaE

CasadevallA

ZaragozaO

2007 Radial mass density, charge, and epitope distribution in the Cryptococcus neoformans capsule. Eukaryot Cell 6 95 109

67. CasadevallA

CleareW

FeldmesserM

Glatman-FreedmanA

GoldmanDL

1998 Characterization of a murine monoclonal antibody to Cryptococcus neoformans polysaccharide that is a candidate for human therapeutic studies. Antimicrob Agents Chemother 42 1437 1446

68. BreimanL

FriedmanJH

OlshenJH

StoneCG

1984 Classification and regression trees. Belmont Wadsworth International

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2010 Číslo 6
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#