KEGG   PATHWAY: ko05140Help
Entry
ko05140                     Pathway                                

Name
Leishmaniasis
Description
Leishmania is an intracellular protozoan parasite of macrophages that causes visceral, mucosal, and cutaneous diseases. The parasite is transmitted to humans by sandflies, where they survive and proliferate intracellularly by deactivating the macrophage. Successful infection of Leishmania is achieved by alteration of signaling events in the host cell, leading to enhanced production of the autoinhibitory molecules like TGF-beta and decreased induction of cytokines such as IL12 for protective immunity. Nitric oxide production is also inhibited. In addition, defective expression of major histocompatibility complex (MHC) genes silences subsequent T cell activation mediated by macrophages, resulting in abnormal immune responses.
Class
09160 Human Diseases; 09167 Infectious diseases
BRITE hierarchy
Pathway map
ko05140  Leishmaniasis
ko05140

Ortholog table
Disease
H00359  Leishmaniasis
Drug
D00582  Sodium stibogluconate (INN)
Orthology
K10159  toll-like receptor 2
K10160  toll-like receptor 4
K04729  myeloid differentiation primary response protein MyD88
K04730  interleukin-1 receptor-associated kinase 1 [EC:2.7.11.1]
K04733  interleukin-1 receptor-associated kinase 4 [EC:2.7.11.1]
K03175  TNF receptor-associated factor 6 [EC:2.3.2.27]
K04427  mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25]
K04403  TAK1-binding protein 1
K04404  TAK1-binding protein 2
K02581  NF-kappa-B inhibitor beta
K04734  NF-kappa-B inhibitor alpha
K02580  nuclear factor NF-kappa-B p105 subunit
K04735  transcription factor p65
K04383  interleukin 1 alpha
K04519  interleukin 1 beta
K05406  interleukin 12A
K05425  interleukin 12B
K03156  tumor necrosis factor superfamily, member 2
K05430  interleukin 4
K13241  nitric-oxide synthase, inducible [EC:1.14.13.39]
K05443  interleukin 10
K13375  transforming growth factor beta-1
K13376  transforming growth factor beta-2
K13377  transforming growth factor beta-3
K03990  complement component 3
K04011  complement component (3b/4b) receptor 1
K06461  integrin alpha M
K06464  integrin beta 2
K06856  immunoglobulin heavy chain
K06498  high affinity immunoglobulin gamma Fc receptor I
K06472  low affinity immunoglobulin gamma Fc receptor II-a
K16824  low affinity immunoglobulin gamma Fc receptor II-c
K06463  low affinity immunoglobulin gamma Fc receptor III
K01404  leishmanolysin [EC:3.4.24.36]
K06483  integrin alpha 4
K05719  integrin beta 1
K11987  prostaglandin-endoperoxide synthase 2 [EC:1.14.99.1]
K19662  classical protein kinase C beta type [EC:2.7.11.13]
K08011  neutrophil cytosolic factor 1
K08010  neutrophil cytosolic factor 2
K08012  neutrophil cytosolic factor 4
K21421  NADPH oxidase 2 [EC:1.-.-.-]
K08009  cytochrome b-245, alpha polypeptide
K04371  mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04375  ETS domain-containing protein Elk-1
K04379  proto-oncogene protein c-fos
K04448  transcription factor AP-1
K04441  p38 MAP kinase [EC:2.7.11.24]
K04687  interferon gamma
K05132  interferon gamma receptor 1
K05133  interferon gamma receptor 2
K11217  Janus kinase 1 [EC:2.7.10.2]
K04447  Janus kinase 2 [EC:2.7.10.2]
K11220  signal transducer and activator of transcription 1
K06752  major histocompatibility complex, class II
K13536  MARCKS-related protein
K13537  cysteine peptidase B [EC:3.4.22.-]
K05697  tyrosine-protein phosphatase non-receptor type 6 [EC:3.1.3.48]
Compound
C00076  Calcium cation
C00195  N-Acylsphingosine
C00219  Arachidonate
C00533  Nitric oxide
C00584  Prostaglandin E2
C02737  Phosphatidylserine
Reference
  Authors
Cunningham AC
  Title
Parasitic adaptive mechanisms in infection by leishmania.
  Journal
Exp Mol Pathol 72:132-41 (2002)
DOI:10.1006/exmp.2002.2418
Reference
  Authors
Nandan D, Knutson KL, Lo R, Reiner NE
  Title
Exploitation of host cell signaling machinery: activation of macrophage phosphotyrosine phosphatases as a novel mechanism of molecular microbial pathogenesis.
  Journal
J Leukoc Biol 67:464-70 (2000)
DOI:10.1002/jlb.67.4.464
Reference
PMID:7591091
  Authors
Nandan D, Reiner NE
  Title
Attenuation of gamma interferon-induced tyrosine phosphorylation in mononuclear phagocytes infected with Leishmania donovani: selective inhibition of signaling through Janus kinases and Stat1.
  Journal
Infect Immun 63:4495-500 (1995)
Reference
  Authors
Nandan D, Lo R, Reiner NE
  Title
Activation of phosphotyrosine phosphatase activity attenuates mitogen-activated protein kinase signaling and inhibits c-FOS and nitric oxide synthase expression in macrophages infected with Leishmania donovani.
  Journal
Infect Immun 67:4055-63 (1999)
Reference
PMID:7916951
  Authors
Reiner NE
  Title
Altered cell signaling and mononuclear phagocyte deactivation during intracellular infection.
  Journal
Immunol Today 15:374-81 (1994)
DOI:10.1016/0167-5699(94)90176-7
Reference
  Authors
Nandan D, Reiner NE
  Title
Leishmania donovani engages in regulatory interference by targeting macrophage protein tyrosine phosphatase SHP-1.
  Journal
Clin Immunol 114:266-77 (2005)
DOI:10.1016/j.clim.2004.07.017
Reference
  Authors
Kima PE
  Title
The amastigote forms of Leishmania are experts at exploiting host cell processes to establish infection and persist.
  Journal
Int J Parasitol 37:1087-96 (2007)
DOI:10.1016/j.ijpara.2007.04.007
Reference
  Authors
Forget G, Gregory DJ, Olivier M
  Title
Proteasome-mediated degradation of STAT1alpha following infection of macrophages with Leishmania donovani.
  Journal
J Biol Chem 280:30542-9 (2005)
DOI:10.1074/jbc.M414126200
Reference
  Authors
Cameron P, McGachy A, Anderson M, Paul A, Coombs GH, Mottram JC, Alexander J, Plevin R
  Title
Inhibition of lipopolysaccharide-induced macrophage IL-12 production by Leishmania mexicana amastigotes: the role of cysteine peptidases and the NF-kappaB signaling pathway.
  Journal
J Immunol 173:3297-304 (2004)
DOI:10.4049/jimmunol.173.5.3297
Reference
  Authors
Tuon FF, Amato VS, Bacha HA, Almusawi T, Duarte MI, Amato Neto V
  Title
Toll-like receptors and leishmaniasis.
  Journal
Infect Immun 76:866-72 (2008)
DOI:10.1128/IAI.01090-07
Reference
  Authors
Kropf P, Freudenberg N, Kalis C, Modolell M, Herath S, Galanos C, Freudenberg M, Muller I
  Title
Infection of C57BL/10ScCr and C57BL/10ScNCr mice with Leishmania major reveals a role for Toll-like receptor 4 in the control of parasite replication.
  Journal
J Leukoc Biol 76:48-57 (2004)
DOI:10.1189/jlb.1003484
Reference
  Authors
Feng GJ, Goodridge HS, Harnett MM, Wei XQ, Nikolaev AV, Higson AP, Liew FY
  Title
Extracellular signal-related kinase (ERK) and p38 mitogen-activated protein (MAP) kinases differentially regulate the lipopolysaccharide-mediated induction of inducible nitric oxide synthase and IL-12 in macrophages: Leishmania phosphoglycans subvert macrophage IL-12 production by targeting ERK MAP kinase.
  Journal
J Immunol 163:6403-12 (1999)
Reference
  Authors
Olivier M, Gregory DJ, Forget G
  Title
Subversion mechanisms by which Leishmania parasites can escape the host immune response: a signaling point of view.
  Journal
Clin Microbiol Rev 18:293-305 (2005)
DOI:10.1128/CMR.18.2.293-305.2005
Reference
  Authors
Matte C, Maion G, Mourad W, Olivier M
  Title
Leishmania donovani-induced macrophages cyclooxygenase-2 and prostaglandin E2 synthesis.
  Journal
Parasite Immunol 23:177-84 (2001)
DOI:10.1046/j.1365-3024.2001.00372.x
Reference
  Authors
Ghosh S, Bhattacharyya S, Sirkar M, Sa GS, Das T, Majumdar D, Roy S, Majumdar S
  Title
Leishmania donovani suppresses activated protein 1 and NF-kappaB activation in host macrophages via ceramide generation: involvement of extracellular signal-regulated kinase.
  Journal
Infect Immun 70:6828-38 (2002)
DOI:10.1128/IAI.70.12.6828-6838.2002
Reference
PMID:9504340
  Authors
Bogdan C, Rollinghoff M
  Title
The immune response to Leishmania: mechanisms of parasite control and evasion.
  Journal
Int J Parasitol 28:121-34 (1998)
DOI:10.1016/S0020-7519(97)00169-0
Reference
  Authors
Blanchette J, Abu-Dayyeh I, Hassani K, Whitcombe L, Olivier M
  Title
Regulation of macrophage nitric oxide production by the protein tyrosine phosphatase Src homology 2 domain phosphotyrosine phosphatase 1 (SHP-1).
  Journal
Immunology 127:123-33 (2009)
DOI:10.1111/j.1365-2567.2008.02929.x
Reference
  Authors
Alexander J, Satoskar AR, Russell DG
  Title
Leishmania species: models of intracellular parasitism.
  Journal
J Cell Sci 112 Pt 18:2993-3002 (1999)
Reference
  Authors
Denkers EY, Butcher BA
  Title
Sabotage and exploitation in macrophages parasitized by intracellular protozoans.
  Journal
Trends Parasitol 21:35-41 (2005)
DOI:10.1016/j.pt.2004.10.004
Reference
  Authors
Lodge R, Diallo TO, Descoteaux A
  Title
Leishmania donovani lipophosphoglycan blocks NADPH oxidase assembly at the phagosome membrane.
  Journal
Cell Microbiol 8:1922-31 (2006)
DOI:10.1111/j.1462-5822.2006.00758.x
Reference
  Authors
de Freitas Balanco JM, Moreira ME, Bonomo A, Bozza PT, Amarante-Mendes G, Pirmez C, Barcinski MA
  Title
Apoptotic mimicry by an obligate intracellular parasite downregulates macrophage microbicidal activity.
  Journal
Curr Biol 11:1870-3 (2001)
DOI:10.1016/S0960-9822(01)00563-2
Reference
  Authors
Kane MM, Mosser DM
  Title
Leishmania parasites and their ploys to disrupt macrophage activation.
  Journal
Curr Opin Hematol 7:26-31 (2000)
Reference
  Authors
de Almeida MC, Vilhena V, Barral A, Barral-Netto M
  Title
Leishmanial infection: analysis of its first steps. A review.
  Journal
Mem Inst Oswaldo Cruz 98:861-70 (2003)
DOI:10.1590/S0074-02762003000700001
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