KEGG   PATHWAY: rbb05140
Entry
rbb05140                    Pathway                                

Name
Leishmaniasis - Rhinopithecus bieti (black snub-nosed monkey)
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
Human Diseases; Infectious disease: parasitic
Pathway map
rbb05140  Leishmaniasis
rbb05140

Organism
Rhinopithecus bieti (black snub-nosed monkey) [GN:rbb]
Gene
108529041  TLR2; toll like receptor 2 [KO:K10159]
108530054  TLR4; toll like receptor 4 [KO:K10160]
108512239  MYD88; myeloid differentiation primary response 88 [KO:K04729]
108535063  IRAK1; interleukin 1 receptor associated kinase 1 [KO:K04730] [EC:2.7.11.1]
108539989  IRAK4; interleukin 1 receptor associated kinase 4 [KO:K04733] [EC:2.7.11.1]
108535559  TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:2.3.2.27]
108539499  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
108520466  TAB1; TGF-beta activated kinase 1 (MAP3K7) binding protein 1 [KO:K04403]
108536673  TAB2; TGF-beta activated kinase 1/MAP3K7 binding protein 2 [KO:K04404]
108539021  NFKBIB; NFKB inhibitor beta [KO:K02581]
108519636  NFKBIA; NFKB inhibitor alpha [KO:K04734]
108532817  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
108543519  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
108541808  IL1A; interleukin 1 alpha [KO:K04383]
108541809  IL1B; interleukin 1 beta [KO:K04519]
108514790  IL12A; interleukin 12A [KO:K05406]
108537933  IL12B; interleukin 12B [KO:K05425]
108520255  TNF; tumor necrosis factor [KO:K03156]
108529583  IL4; interleukin 4 [KO:K05430]
108539959  NOS2; nitric oxide synthase 2 [KO:K13241] [EC:1.14.13.39]
108535116  IL10; interleukin 10 [KO:K05443]
108536158  TGFB1; transforming growth factor beta 1 [KO:K13375]
108528282  TGFB2; transforming growth factor beta 2 [KO:K13376]
108534939  TGFB3; transforming growth factor beta 3 [KO:K13377]
108534593  C3; complement C3 [KO:K03990]
108530296  complement receptor type 1-like [KO:K04011]
108539535  complement component receptor 1-like protein [KO:K04011]
108539534  CR1; complement C3b/C4b receptor 1 (Knops blood group) [KO:K04011]
108528119  ITGAM; integrin subunit alpha M [KO:K06461]
108539787  ITGB2; integrin subunit beta 2 [KO:K06464]
108522153  putative V-set and immunoglobulin domain-containing-like protein IGHV4OR15-8 [KO:K06856]
108511997  putative V-set and immunoglobulin domain-containing-like protein IGHV4OR15-8 [KO:K06856]
108512001  putative V-set and immunoglobulin domain-containing-like protein IGHV4OR15-8 [KO:K06856]
108520828  uncharacterized LOC108520828 [KO:K06856]
108519975  uncharacterized LOC108519975 [KO:K06856]
108519976  uncharacterized LOC108519976 [KO:K06856]
108519983  uncharacterized LOC108519983 [KO:K06856]
108519992  putative V-set and immunoglobulin domain-containing-like protein IGHV4OR15-8 [KO:K06856]
108524775  putative V-set and immunoglobulin domain-containing-like protein IGHV4OR15-8 [KO:K06856]
108538696  high affinity immunoglobulin gamma Fc receptor I [KO:K06498]
108542586  FCGR2A; Fc fragment of IgG receptor IIa [KO:K06472]
108542585  low affinity immunoglobulin gamma Fc region receptor III-like [KO:K06463]
108526617  integrin alpha-4 [KO:K06483]
108529400  ITGB1; integrin subunit beta 1 [KO:K05719]
108523178  PTGS2; prostaglandin-endoperoxide synthase 2 [KO:K11987] [EC:1.14.99.1]
108538857  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
108513939  NCF1; neutrophil cytosolic factor 1 [KO:K08011]
108512725  NCF2; neutrophil cytosolic factor 2 [KO:K08010]
108518478  NCF4; neutrophil cytosolic factor 4 [KO:K08012]
108522897  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
108520444  cytochrome b-245 light chain [KO:K08009]
108523695  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
108536070  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
108530915  ELK1; ELK1, ETS transcription factor [KO:K04375]
108534930  FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
108532921  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
108528326  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
108528327  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
108539403  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
108539422  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
108532274  IFNG; interferon gamma [KO:K04687]
108522967  IFNGR1; interferon gamma receptor 1 [KO:K05132]
108536857  IFNGR2; interferon gamma receptor 2 [KO:K05133]
108532886  JAK1; Janus kinase 1 [KO:K11217] [EC:2.7.10.2]
108523026  tyrosine-protein kinase JAK2-like [KO:K04447] [EC:2.7.10.2]
108527866  STAT1; signal transducer and activator of transcription 1 [KO:K11220]
108540290  HLA class II histocompatibility antigen, DP beta 1 chain-like [KO:K06752]
108540291  HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752]
108540294  HLA class II histocompatibility antigen, DP alpha 1 chain [KO:K06752]
108512973  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
108512974  HLA class II histocompatibility antigen, DM alpha chain [KO:K06752]
108512982  HLA class II histocompatibility antigen, DO beta chain [KO:K06752]
108512983  HLA class II histocompatibility antigen, DQ beta 1 chain [KO:K06752]
108512984  HLA class II histocompatibility antigen, DQ alpha 1 chain [KO:K06752]
108512985  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
108519881  mamu class II histocompatibility antigen, DR alpha chain [KO:K06752]
108519884  HLA class II histocompatibility antigen, DRB1-13 beta chain [KO:K06752]
108519885  HLA class II histocompatibility antigen, DR beta 5 chain [KO:K06752]
108524016  MARCKSL1; MARCKS like 1 [KO:K13536]
108538073  elongation factor 1-alpha 1 [KO:K03231]
108529199  EEF1A1; eukaryotic translation elongation factor 1 alpha 1 [KO:K03231]
108541857  putative elongation factor 1-alpha-like 3 [KO:K03231]
108535300  EEF1A2; eukaryotic translation elongation factor 1 alpha 2 [KO:K03231]
108542024  PTPN6; protein tyrosine phosphatase, non-receptor type 6 [KO:K05697] [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)
DOI:10.1128/IAI.63.11.4495-4500.1995
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)
DOI:10.1128/IAI.67.8.4055-4063.1999
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)
DOI:10.1097/00062752-200001000-00006
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
Related
pathway
rbb00590  Arachidonic acid metabolism
rbb04010  MAPK signaling pathway
rbb04020  Calcium signaling pathway
rbb04120  Ubiquitin mediated proteolysis
rbb04145  Phagosome
rbb04610  Complement and coagulation cascades
rbb04620  Toll-like receptor signaling pathway
rbb04630  JAK-STAT signaling pathway
rbb04666  Fc gamma R-mediated phagocytosis
KO pathway
ko05140   
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