Sex and Death: The Effects of Innate Immune Factors on the Sexual Reproduction of Malaria Parasites
Malaria parasites must undergo a round of sexual reproduction in the blood meal of a mosquito vector to be transmitted between hosts. Developing a transmission-blocking intervention to prevent parasites from mating is a major goal of biomedicine, but its effectiveness could be compromised if parasites can compensate by simply adjusting their sex allocation strategies. Recently, the application of evolutionary theory for sex allocation has been supported by experiments demonstrating that malaria parasites adjust their sex ratios in response to infection genetic diversity, precisely as predicted. Theory also predicts that parasites should adjust sex allocation in response to host immunity. Whilst data are supportive, the assumptions underlying this prediction – that host immune responses have differential effects on the mating ability of males and females – have not yet been tested. Here, we combine experimental work with theoretical models in order to investigate whether the development and fertility of male and female parasites is affected by innate immune factors and develop new theory to predict how parasites' sex allocation strategies should evolve in response to the observed effects. Specifically, we demonstrate that reactive nitrogen species impair gametogenesis of males only, but reduce the fertility of both male and female gametes. In contrast, tumour necrosis factor-α does not influence gametogenesis in either sex but impairs zygote development. Therefore, our experiments demonstrate that immune factors have complex effects on each sex, ranging from reducing the ability of gametocytes to develop into gametes, to affecting the viability of offspring. We incorporate these results into theory to predict how the evolutionary trajectories of parasite sex ratio strategies are shaped by sex differences in gamete production, fertility and offspring development. We show that medical interventions targeting offspring development are more likely to be ‘evolution-proof’ than interventions directed at killing males or females. Given the drive to develop medical interventions that interfere with parasite mating, our data and theoretical models have important implications.
Vyšlo v časopise:
Sex and Death: The Effects of Innate Immune Factors on the Sexual Reproduction of Malaria Parasites. PLoS Pathog 7(3): e32767. doi:10.1371/journal.ppat.1001309
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1001309
Souhrn
Malaria parasites must undergo a round of sexual reproduction in the blood meal of a mosquito vector to be transmitted between hosts. Developing a transmission-blocking intervention to prevent parasites from mating is a major goal of biomedicine, but its effectiveness could be compromised if parasites can compensate by simply adjusting their sex allocation strategies. Recently, the application of evolutionary theory for sex allocation has been supported by experiments demonstrating that malaria parasites adjust their sex ratios in response to infection genetic diversity, precisely as predicted. Theory also predicts that parasites should adjust sex allocation in response to host immunity. Whilst data are supportive, the assumptions underlying this prediction – that host immune responses have differential effects on the mating ability of males and females – have not yet been tested. Here, we combine experimental work with theoretical models in order to investigate whether the development and fertility of male and female parasites is affected by innate immune factors and develop new theory to predict how parasites' sex allocation strategies should evolve in response to the observed effects. Specifically, we demonstrate that reactive nitrogen species impair gametogenesis of males only, but reduce the fertility of both male and female gametes. In contrast, tumour necrosis factor-α does not influence gametogenesis in either sex but impairs zygote development. Therefore, our experiments demonstrate that immune factors have complex effects on each sex, ranging from reducing the ability of gametocytes to develop into gametes, to affecting the viability of offspring. We incorporate these results into theory to predict how the evolutionary trajectories of parasite sex ratio strategies are shaped by sex differences in gamete production, fertility and offspring development. We show that medical interventions targeting offspring development are more likely to be ‘evolution-proof’ than interventions directed at killing males or females. Given the drive to develop medical interventions that interfere with parasite mating, our data and theoretical models have important implications.
Zdroje
1. PaulREL
ArieyF
RobertV
2003 The evolutionary ecology of Plasmodium. Ecol Lett 6 866 880
2. SaulA
2008 Efficacy model for mosquito stage transmission blocking vaccines for malaria. Parasitology 135 1497 1506
3. SmithDL
McKenzieFE
SnowRW
HaySI
2007 Revisiting the basic reproductive number for malaria and its implications for malaria control. PLoS Biol 5 531 542
4. van DijkMR
van SchaijkBCL
KhanSM
van DoorenMW
RamesarJ
2010 Three members of the 6-cys protein family of Plasmodium play a role in gamete fertility. PLoS Pathog 6 e1000853
5. CarterR
2001 Transmission blocking malaria vaccines. Vaccine 19 2309 2314
6. van DijkMR
JanseCJ
ThompsonJ
WatersAP
BraksJAM
2001 A central role for P48/45 in malaria parasite male gamete fertility. Cell 104 153 164
7. OutchkourovNS
RoeffenW
KaanA
JansenJ
LutyA
2008 Correctly folded Pfs48/45 protein of Plasmodium falciparum elicits malaria transmission-blocking immunity in mice. Proc Natl Acad Sci U S A 105 4301 4305
8. ChowdhuryDR
AngovE
KariukiT
KumarN
2009 A potent malaria transmission blocking vaccine based on codon harmonized full length Pfs48/45 expressed in Escherichia coli. PLoS One 4 e6352
9. WestSA
2010 Sex allocation New Jersey Princeton University Press
10. TaylorLH
ReadAF
1997 Why so few transmission stages? Reproductive restraint by malaria parasites. Parasitol Today 13 135 140
11. TalmanAM
DomarleO
McKenzieFE
ArieyF
RobertV
2004 Gametocytogenesis: the puberty of Plasmodium falciparum. Malaria J 3 24
12. AlanoP
CarterR
1990 Sexual differentiation in malaria parasites. Annu Rev Microbiol 44 429 449
13. VaughanJA
2007 Population dynamics of Plasmodium sporogony. Trends Parasitol 23 63 70
14. WestSA
ReeceSE
ReadAF
2001 Evolution of gametocyte sex ratios in malaria and related apicomplexan (protozoan) parasites. Trends Parasitol 17 525 531
15. GardnerA
ReeceSE
WestSA
2003 Even more extreme fertility insurance and the sex ratios of protozoan blood parasites. J Theor Biol 223 515 521
16. JanseCJ
VanderkloosterPFJ
VanderkaayHJ
VanderploegM
OverdulveJP
1986 Rapid repeated DNA replication during microgametogenesis and DNA synthesis in young zygotes of Plasmodium berghei. Trans R Soc Trop Med Hyg 80 154 157
17. SindenRE
1998 Gametocytes and sexual development.
ShermanIW
Malaria: Parasite Biology, Pathogenesis and Protection Washington DC ASM Press 25 48
18. SindenRE
1983 Sexual development of malarial parasites. Adv Parasit 22 153 216
19. ReeceSE
DrewDR
GardnerA
2008 Sex ratio adjustment and kin discrimination in malaria parasites. Nature 453 609 615
20. SchallJJ
2000 Transmission success of the malaria parasite Plasmodium mexicanum into its vector: role of gametocyte density and sex ratio. Parasitology 121 575 580
21. MonsB
1986 Intra erythrocytic differentiation of Plasmodium berghei. Acta Leiden 54 1 124
22. KhanSM
Franke-FayardB
MairGR
LasonderE
JanseCJ
2005 Proteome analysis of separated male and female gametocytes reveals novel sex-specific Plasmodium biology. Cell 121 675 687
23. SindenRE
1983 The cell biology of sexual development in Plasmodium. Parasitology 86 7 28
24. MairGR
LasonderE
GarverLS
Franke-FayardBMD
CarretCK
2010 Universal features of post-transcriptional gene regulation are critical for Plasmodium zygote development. PLoS Pathog 6 e1000767
25. JanseCJ
WatersAP
2004 Sexual development of malaria parasites.
JanseCJ
WatersAP
Malaria parasites, genomes and molecular biology Wymondham, United Kingdom Caister Academic Press 445 474
26. PaulREL
CoulsonTN
RaibaudA
BreyPT
2000 Sex determination in malaria parasites. Science 287 128 131
27. ReeceSE
RamiroRS
NusseyDH
2009 Plastic parasites: sophisticated strategies for survival and reproduction?. Evol Appl 2 11 23
28. MitriC
ThieryI
BourgouinC
PaulREL
2009 Density-dependent impact of the human malaria parasite Plasmodium falciparum gametocyte sex ratio on mosquito infection rates. Proc Biol Sci 276 3721 3726
29. NeeS
WestSA
ReadAF
2002 Inbreeding and parasite sex ratios. Proc Biol Sci 269 755 760
30. HamiltonWD
1967 Extraordinary sex ratios. Science 156 477 488
31. WestSA
SmithTG
NeeS
ReadAF
2002 Fertility insurance and the sex ratios of malaria and related hemospororin blood parasites. J Parasitol 88 258 263
32. ReadAF
NararaA
NeeS
KeymerAE
DayKP
1992 Gametocyte sex ratios as indirect measures of outcrossing rates in malaria. Parasitology 104 387 395
33. WestSA
SmithTG
ReadAF
2000 Sex allocation and population structure in apicomplexan (protozoa) parasites. Proc Biol Sci 267 257 263
34. ReadAF
AnwarM
ShutlerD
NeeS
1995 Sex allocation and population structure in malaria and related parasitic protozoa. Proc Biol Sci 260 359 363
35. CarterR
GwadzRW
GreenI
1979 Plasmodium gallinaceum: transmission-blocking immunity in chickens. II. Effect of anti-gamete antibodies in-vitro and in-vivo and their elaboration during infection. Exp Parasitol 47 194 208
36. NaotunneTS
KarunaweeraND
Del GiudiceG
KularatneMU
GrauGE
1991 Cytokines kill malaria parasites during infection crisis: extracellular complementary factors are essential. J Exp Med 173 523 529
37. NaotunneTD
KarunaweeraND
MendisKN
CarterR
1993 Cytokine-mediated inactivation of malarial gametocytes is dependent on the presence of white blood-cells and involves reactive nitrogen intermediates. Immunology 78 555 562
38. DrakeleyCJ
MulderL
TchuinkamT
GuptaS
SauerweinR
1998 Transmission-blocking effects of sera from malaria-exposed individuals on Plasmodium falciparum isolates from gametocyte carriers. Parasitology 116 417 423
39. TargettGAT
1988 Plasmodium falciparum: natural and experimental transmission-blocking immunity. Immunol Lett 19 235 240
40. MendisKN
MunesingheYD
DesilvaYNY
KeragallaI
CarterR
1987 Malaria transmission-blocking immunity induced by natural infections of Plasmodium vivax in humans. Infect Immun 55 369 372
41. LongGH
ChanBHK
AllenJE
ReadAF
GrahamAL
2008 Blockade of TNF receptor 1 reduces disease severity but increases parasite transmission during Plasmodium chabaudi chabaudi infection. Int J Parasitol 38 1073 1081
42. CaoY-M
TsuboiT
ToriiM
1998 Nitric oxide inhibits the development of Plasmodium yoelii gametocytes into gametes. Parasitol Int 47 157 166
43. MendisC
TargettGAT
1981 Immunization to produce a transmission blocking immunity in Plasmodium yoelii malaria infections. Trans R Soc Trop Med Hyg 75 158 159
44. LuckhartS
VodovotzY
CuiLW
RosenbergR
1998 The mosquito Anopheles stephensi limits malaria parasite development with inducible synthesis of nitric oxide. Proc Natl Acad Sci U S A 95 5700 5705
45. KarunaweeraND
CarterR
GrauGE
KwiatkowskiD
DelgiudiceG
1992 Tumor necrosis factor-dependent parasite-killing effects during paroxysms in nonimmune Plasmodium vivax malaria patients. Clin Exp Immunol 88 499 505
46. TraceyKJ
CeramiA
1994 Tumor necrosis factor: a pleiotropic cytokine and therapeutic target. Annu Rev Med 45 491 503
47. Muniz-JunqueiraMI
dos Santos-NetoLL
TostaCE
2001 Influence of tumor necrosis factor-alpha on the ability of monocytes and lymphocytes to destroy intraerythrocytic Plasmodium falciparum in vitro. Cell Immunol 208 73 79
48. LensenAHW
Bolmer-Van de VegteM
vanGemertGJ
ElingWMC
SauerweinRW
1997 Leukocytes in a Plasmodium falciparum-infected blood meal reduce transmission of malaria to Anopheles mosquitoes. Infect Immun 65 3834 3837
49. MotardA
LandauI
NusslerA
GrauG
BaccamD
1993 The role of reactive nitrogen intermediates in modulation of gametocyte infectivity of rodent malaria parasites. Parasite Immunol 15 21 26
50. BogdanC
2001 Nitric oxide and the immune response. Nat Immunol 2 907 916
51. WangQH
LiuYJ
LiuJ
ChenG
ZhengW
2009 Plasmodium yoelii: Assessment of production and role of nitric oxide during the early stages of infection in susceptible and resistant mice. Exp Parasitol 121 268 273
52. AliM
Al-OlayanEM
LewisS
MatthewsH
HurdH
2010 Naturally occurring triggers that induce apoptosis-like programmed cell death in Plasmodium berghei ookinetes. PLoS One 5 e12634
53. LuckhartS
CramptonAL
ZamoraR
LieberMJ
Dos SantosPC
2003 Mammalian transforming growth factor beta 1 activated after ingestion by Anopheles stephensi modulates mosquito immunity. Infect Immun 71 3000 3009
54. SinghRJ
HoggN
JosephJ
KonorevE
KalyanaramanB
1999 The peroxynitrite generator, SIN-1, becomes a nitric oxide donor in the presence of electron acceptors. Arch Biochem Biophys 361 331 339
55. Dea-AyuelaMA
Ordonez-GutierrezL
Bolas-FernandezF
2009 Changes in the proteome and infectivity of Leishmania infantum induced by in vitro exposure to a nitric oxide donor. Int J Med Microbiol 299 221 232
56. Maynard SmithJ
1982 Evolution and the theory of games Cambridge Cambridge University Press
57. Maynard SmithJ
PriceGR
1973 The logic of animal conflict. Nature 246 15 18
58. TaylorPD
1996 Inclusive fitness arguments in genetic models of behaviour. J Math Biol 34 654 674
59. ClarkIA
RockettKA
1996 Nitric oxide and parasitic disease. Adv Parasit 37 1 56
60. de Koning-WardTF
OlivieriA
BertucciniL
HoodA
SilvestriniF
2008 The role of osmiophilic bodies and Pfg377 expression in female gametocyte emergence and mosquito infectivity in the human malaria parasite Plasmodium falciparum. Mol Microbiol 67 278 290
61. HurdH
CarterV
2004 The role of programmed cell death in Plasmodium mosquito interactions. Int J Parasitol 34 1459 1472
62. JanseCJ
MonsB
RouwenhorstRJ
VanderkloosterPFJ
OverdulveJP
1985 In vitro formation of ookinetes and functional maturity of Plasmodium berghei gametocytes. Parasitology 91 19 29
63. MairGR
BraksJAM
GarverLS
WiegantJCAG
HallN
2006 Regulation of sexual development of Plasmodium by translational repression. Science 313 667 669
64. DrakeleyC
SutherlandC
BousernaJT
SauerweinRW
TargettGAT
2006 The epidemiology of Plasmodium falciparum gametocytes: weapons of mass dispersion. Trends Parasitol 22 424 430
65. ReeceSE
AliE
SchneiderP
BabikerHA
2010 Stress, drugs and the evolution of reproductive restraint in malaria parasites. Proc Biol Sci 277 3123 3129
66. MideoN
DayT
2008 On the evolution of reproductive restraint in malaria. Proc Biol Sci 275 1217 1224
67. SaxenaAK
WuY
GarbocziDN
2007 Plasmodium P25 and P28 surface proteins: potential transmission-blocking vaccines. Eukaryot cell 6 1260 1265
68. PonziM
Siden-KiamosI
BertucciniL
CurraC
KroezeH
2009 Egress of Plasmodium berghei gametes from their host erythrocyte is mediated by the MDV-1/PEG3 protein. Cell Microbiol 11 1272 1288
69. GautretP
CoquelinF
ChabaudAG
LandauI
1997 The production of gametocytes by rodent Plasmodium species in mice during phenylhydrazine induced reticulocytosis. Acta Parasitol 42 65 67
70. NoackE
FeelischM
1989 Molecular aspects underlying the vasodilator action of molsidomine. J Cardiovasc Pharm 14 S1 S5
71. FeelischM
OstrowskiJ
NoackE
1989 On the mechanism of NO release from sydnonimines. J Cardiovasc Pharm 14 S13 S22
72. NovoE
ParolaM
2008 Redox mechanisms in hepatic chronic wound healing and fibrogenesis. Fibrogenesis Tissue Repair 1 5
73. KawamotoF
KidoN
HanaichiT
DjamgozMBA
SindenRE
1992 Gamete development in Plasmodium berghei regulated by ionic exchange mechanisms. Parasitol Res 78 277 284
74. KawamotoF
AlejoblancoR
FleckSL
SindenRE
1991 Plasmodium berghei: ionic regulation and the induction of gametogenesis. Exp Parasitol 72 33 42
75. ReeceSE
DuncanAB
WestSA
ReadAF
2003 Sex ratios in the rodent malaria parasite, Plasmodium chabaudi. Parasitology 127 419 425
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Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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