KEGG   PATHWAY: hsa05144
Entry
hsa05144                    Pathway                                
Name
Malaria - Homo sapiens (human)
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
hsa05144  Malaria
hsa05144

Disease
H00361  Malaria
Organism
Homo sapiens (human) [GN:hsa]
Gene
100528032  KLRC4-KLRK1; KLRC4-KLRK1 readthrough [KO:K06728]
1311  COMP; cartilage oligomeric matrix protein [KO:K04659]
1378  CR1; complement C3b/C4b receptor 1 (Knops blood group) [KO:K04011]
1379  CR1L; complement C3b/C4b receptor 1 like [KO:K04011]
1440  CSF3; colony stimulating factor 3 [KO:K05423]
22914  KLRK1; killer cell lectin like receptor K1 [KO:K06728]
2532  ACKR1; atypical chemokine receptor 1 (Duffy blood group) [KO:K06574]
2993  GYPA; glycophorin A (MNS blood group) [KO:K06575]
2994  GYPB; glycophorin B (MNS blood group) [KO:K20925]
2995  GYPC; glycophorin C (Gerbich blood group) [KO:K06576]
3039  HBA1; hemoglobin subunit alpha 1 [KO:K13822]
3040  HBA2; hemoglobin subunit alpha 2 [KO:K13822]
3043  HBB; hemoglobin subunit beta [KO:K13823]
3082  HGF; hepatocyte growth factor [KO:K05460]
3383  ICAM1; intercellular adhesion molecule 1 [KO:K06490]
3458  IFNG; interferon gamma [KO:K04687]
3553  IL1B; interleukin 1 beta [KO:K04519]
3569  IL6; interleukin 6 [KO:K05405]
3576  CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030]
3586  IL10; interleukin 10 [KO:K05443]
3592  IL12A; interleukin 12A [KO:K05406]
3606  IL18; interleukin 18 [KO:K05482]
3683  ITGAL; integrin subunit alpha L [KO:K05718]
3689  ITGB2; integrin subunit beta 2 [KO:K06464]
3820  KLRB1; killer cell lectin like receptor B1 [KO:K06543]
4035  LRP1; LDL receptor related protein 1 [KO:K04550]
4233  MET; MET proto-oncogene, receptor tyrosine kinase [KO:K05099] [EC:2.7.10.1]
4615  MYD88; MYD88 innate immune signal transduction adaptor [KO:K04729]
5175  PECAM1; platelet and endothelial cell adhesion molecule 1 [KO:K06471]
54106  TLR9; toll like receptor 9 [KO:K10161]
6347  CCL2; C-C motif chemokine ligand 2 [KO:K14624]
6382  SDC1; syndecan 1 [KO:K06257]
6383  SDC2; syndecan 2 [KO:K16336]
6401  SELE; selectin E [KO:K06494]
6403  SELP; selectin P [KO:K06496]
7040  TGFB1; transforming growth factor beta 1 [KO:K13375]
7042  TGFB2; transforming growth factor beta 2 [KO:K13376]
7043  TGFB3; transforming growth factor beta 3 [KO:K13377]
7057  THBS1; thrombospondin 1 [KO:K16857]
7058  THBS2; thrombospondin 2 [KO:K04659]
7059  THBS3; thrombospondin 3 [KO:K04659]
7060  THBS4; thrombospondin 4 [KO:K04659]
7097  TLR2; toll like receptor 2 [KO:K10159]
7099  TLR4; toll like receptor 4 [KO:K10160]
7124  TNF; tumor necrosis factor [KO:K03156]
7412  VCAM1; vascular cell adhesion molecule 1 [KO:K06527]
948  CD36; CD36 molecule [KO:K06259]
958  CD40; CD40 molecule [KO:K03160]
959  CD40LG; CD40 ligand [KO:K03161]
975  CD81; CD81 molecule [KO:K06508]
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
hsa04210  Apoptosis
hsa04514  Cell adhesion molecules
hsa04610  Complement and coagulation cascades
hsa04620  Toll-like receptor signaling pathway
KO pathway
ko05144   

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