KEGG   PATHWAY: ko05144
Entry
ko05144                     Pathway                                
Name
Malaria
Description
Plasmodium protozoa are parasites that account for malaria infection. Sporozoite forms of the parasite are injected by mosquito bites under the skin and are carried to the liver where they develop into the merozoite form.
Sporozoite invasion of hepatocytes is mediated by parasite surface protein like CSP. Subsequent infection into red blood cells (RBCs) by merozoites causes malaria disease via aberrant cytokine production and sequestration of parasite-infected red blood cells (pRBCs) to host endothelium. Microvasculature sequestration in the brain brings about cerebral malaria that can results in death or persisting neurological impairment. PfEMP1 has been suggested as the key adhesive molecule of pRBCs.
Class
Human Diseases; Infectious disease: parasitic
Pathway map
ko05144  Malaria
ko05144

Disease
H00361  Malaria
Orthology
K13833  sporozoite microneme protein
K13834  sporozoite microneme protein 2
K13835  cell-traversal protein for ookinetes and sporozoites
K13836  circumsporozoite protein
K06257  syndecan 1
K16336  syndecan 2
K13837  thrombospondin-related anonymous protein
K04550  low-density lipoprotein receptor-related protein 1 (alpha-2-macroglobulin receptor)
K06508  CD81 antigen
K05460  hepatocyte growth factor
K05099  proto-oncogene tyrosine-protein kinase Met [EC:2.7.10.1]
K13838  merozoite surface protein 1
K13839  merozoite surface protein 2
K13840  merozoite surface protein 3
K13841  merozoite surface protein 4
K13842  merozoite surface protein 5
K13843  merozoite surface protein 6
K13844  merozoite surface protein 8
K13845  apical merozoite antigen 1
K13846  Duffy binding protein
K06574  atypical chemokine receptor 1
K13847  erythrocyte-binding antigen 175
K06575  glycophorin A
K20925  glycophorin B
K13848  erythrocyte-binding antigen 140
K06576  glycophorin C
K13849  reticulocyte-binding protein
K13822  hemoglobin subunit alpha
K13823  hemoglobin subunit beta
K13850  erythrocyte membrane protein 1
K13851  repetitive interspersed family protein
K13852  subtelomeric variable open reading frame
K10161  toll-like receptor 9
K04729  myeloid differentiation primary response protein MyD88
K10159  toll-like receptor 2
K10160  toll-like receptor 4
K05443  interleukin 10
K13375  transforming growth factor beta-1
K13376  transforming growth factor beta-2
K13377  transforming growth factor beta-3
K10030  interleukin 8
K05405  interleukin 6
K14624  C-C motif chemokine 2
K05423  granulocyte colony-stimulating factor
K04519  interleukin 1 beta
K03156  tumor necrosis factor superfamily, member 2
K05406  interleukin 12A
K05482  interleukin 18
K06543  killer cell lectin-like receptor subfamily B
K06728  killer cell lectin-like receptor subfamily K member 1
K23459  killer cell lectin-like receptor subfamily A member 4
K10784  T cell receptor alpha chain V region
K10785  T-cell receptor beta chain V region
K04687  interferon gamma
K06259  CD36 antigen
K04011  complement component (3b/4b) receptor 1
K06471  platelet/endothelial cell adhesion molecule
K06527  vascular cell adhesion molecule 1
K16857  thrombospondin 1
K04659  thrombospondin 2/3/4/5
K06494  selectin, endothelial cell
K05718  integrin alpha L
K06464  integrin beta 2
K06490  intercellular adhesion molecule 1
K03161  tumor necrosis factor ligand superfamily member 5
K03160  tumor necrosis factor receptor superfamily member 5
K06496  selectin, platelet
Compound
C00533  Nitric oxide
C00634  Chondroitin 4-sulfate
G00052  Type II B antigen
G00054  Type II A antigen
G10505  Hyaluronic acid
Reference
PMID:19101208
  Authors
Morahan BJ, Wang L, Coppel RL
  Title
No TRAP, no invasion.
  Journal
Trends Parasitol 25:77-84 (2009)
DOI:10.1016/j.pt.2008.11.004
Reference
PMID:8920859
  Authors
Shakibaei M, Frevert U
  Title
Dual interaction of the malaria circumsporozoite protein with the low density lipoprotein receptor-related protein (LRP) and heparan sulfate proteoglycans.
  Journal
J Exp Med 184:1699-711 (1996)
DOI:10.1084/jem.184.5.1699
Reference
PMID:15106591
  Authors
Silvie O, Franetich JF, Renia L, Mazier D
  Title
Malaria sporozoite: migrating for a living.
  Journal
Trends Mol Med 10:97-100; discussion 100-1 (2004)
DOI:10.1016/j.molmed.2004.01.004
Reference
PMID:15464448
  Authors
Mota MM, Giordano S, Rodriguez A
  Title
Targeting Plasmodium host cells: survival within hepatocytes.
  Journal
Trends Mol Med 10:487-92 (2004)
DOI:10.1016/j.molmed.2004.08.003
Reference
PMID:12364790
  Authors
Cowman AF, Crabb BS
  Title
The Plasmodium falciparum genome--a blueprint for erythrocyte invasion.
  Journal
Science 298:126-8 (2002)
DOI:10.1126/science.1078169
Reference
PMID:16019257
  Authors
O'Donnell RA, Blackman MJ
  Title
The role of malaria merozoite proteases in red blood cell invasion.
  Journal
Curr Opin Microbiol 8:422-7 (2005)
DOI:10.1016/j.mib.2005.06.018
Reference
PMID:17630968
  Authors
Iyer J, Gruner AC, Renia L, Snounou G, Preiser PR
  Title
Invasion of host cells by malaria parasites: a tale of two protein families.
  Journal
Mol Microbiol 65:231-49 (2007)
DOI:10.1111/j.1365-2958.2007.05791.x
Reference
PMID:11224682
  Authors
Chitnis CE
  Title
Molecular insights into receptors used by malaria parasites for erythrocyte invasion.
  Journal
Curr Opin Hematol 8:85-91 (2001)
DOI:10.1097/00062752-200103000-00005
Reference
PMID:15094163
  Authors
Rasti N, Wahlgren M, Chen Q
  Title
Molecular aspects of malaria pathogenesis.
  Journal
FEMS Immunol Med Microbiol 41:9-26 (2004)
DOI:10.1016/j.femsim.2004.01.010
Reference
PMID:15463497
  Authors
Clark IA, Rockett KA, Cowden WB
  Title
Proposed link between cytokines, nitric oxide and human cerebral malaria.
  Journal
Parasitol Today 7:205-7 (1991)
DOI:10.1016/0169-4758(91)90142-B
Reference
PMID:18250459
  Authors
Hisaeda H, Tetsutani K, Imai T, Moriya C, Tu L, Hamano S, Duan X, Chou B, Ishida H, Aramaki A, Shen J, Ishii KJ, Coban C, Akira S, Takeda K, Yasutomo K, Torii M, Himeno K
  Title
Malaria parasites require TLR9 signaling for immune evasion by activating regulatory T cells.
  Journal
J Immunol 180:2496-503 (2008)
DOI:10.4049/jimmunol.180.4.2496
Reference
PMID:10885986
  Authors
Chen Q, Schlichtherle M, Wahlgren M
  Title
Molecular aspects of severe malaria.
  Journal
Clin Microbiol Rev 13:439-50 (2000)
DOI:10.1128/CMR.13.3.439-450.2000
Reference
PMID:11832955
  Authors
Miller LH, Baruch DI, Marsh K, Doumbo OK
  Title
The pathogenic basis of malaria.
  Journal
Nature 415:673-9 (2002)
DOI:10.1038/415673a
Reference
PMID:19967139
  Authors
Faille D, El-Assaad F, Alessi MC, Fusai T, Combes V, Grau GE
  Title
Platelet-endothelial cell interactions in cerebral malaria: the end of a cordial understanding.
  Journal
Thromb Haemost 102:1093-102 (2009)
DOI:10.1160/TH09-05-0337
Reference
PMID:16138104
  Authors
Schofield L, Grau GE
  Title
Immunological processes in malaria pathogenesis.
  Journal
Nat Rev Immunol 5:722-35 (2005)
DOI:10.1038/nri1686
Reference
PMID:14737184
  Authors
Ishino T, Yano K, Chinzei Y, Yuda M
  Title
Cell-passage activity is required for the malarial parasite to cross the liver sinusoidal cell layer.
  Journal
PLoS Biol 2:E4 (2004)
DOI:10.1371/journal.pbio.0020004
Reference
PMID:16468982
  Authors
Kariu T, Ishino T, Yano K, Chinzei Y, Yuda M
  Title
CelTOS, a novel malarial protein that mediates transmission to mosquito and vertebrate hosts.
  Journal
Mol Microbiol 59:1369-79 (2006)
DOI:10.1111/j.1365-2958.2005.05024.x
Reference
PMID:20091081
  Authors
Cox D, McConkey S
  Title
The role of platelets in the pathogenesis of cerebral malaria.
  Journal
Cell Mol Life Sci 67:557-68 (2010)
DOI:10.1007/s00018-009-0211-3
Related
pathway
ko04210  Apoptosis
ko04514  Cell adhesion molecules
ko04610  Complement and coagulation cascades
ko04620  Toll-like receptor signaling pathway
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