title: Distinct genetic control of parasite elimination, dissemination, and disease after Leishmania major infection.
abstract: Elimination of pathogens is the basis of host resistance to infections; however, relationship between persisting pathogens and disease has not been clarified. Leishmania major infection in mice is an important model of host-pathogen relationship. Infected BALB/c mice exhibit high parasite numbers in lymph nodes and spleens, and a chronic disease with skin lesions, splenomegaly, and hepatomegaly, increased serum IgE levels and cytokine imbalance. Although numerous gene loci affecting these disease symptoms have been reported, genes controlling parasites' elimination or dissemination have never been mapped. We therefore compared genetics of the clinical and immunologic symptomatology with parasite load in (BALB/c x CcS-11) F2 hybrids and mapped five loci, two of which control parasite elimination or dissemination. Lmr5 influences parasite loads in spleens (and skin lesions, splenomegaly, and serum IgE, IL-4, and IFNgamma levels), and Lmr20 determines parasite numbers in draining lymph nodes (and serum levels of IgE and IFNgamma), but no skin or visceral pathology. Three additional loci do not affect parasite numbers but influence significantly the disease phenotype-Lmr21: skin lesions and IFNgamma levels, Lmr22: IL-4 levels, Lmr23: IFNgamma levels, indicating that development of L. major-caused disease includes critical regulations additional to control of parasite spread.
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídenská 1083, 142 20 Prague 4, Czech Republic.
authors.forename: Iryna
authors.initials: I
authors.lastname: Kurey
authors.forename: Tetyana
authors.initials: T
authors.lastname: Kobets
authors.forename: Helena
authors.initials: H
authors.lastname: Havelková
authors.forename: Martina
authors.initials: M
authors.lastname: Slapnicková
authors.forename: Lei
authors.initials: L
authors.lastname: Quan
authors.forename: Katerina
authors.initials: K
authors.lastname: Trtková
authors.forename: Igor
authors.initials: I
authors.lastname: Grekov
authors.forename: Milena
authors.initials: M
authors.lastname: Svobodová
authors.forename: Alphons P
authors.initials: AP
authors.lastname: Stassen
authors.forename: Alan
authors.initials: A
authors.lastname: Hutson
authors.forename: Peter
authors.initials: P
authors.lastname: Demant
authors.forename: Marie
authors.initials: M
authors.lastname: Lipoldová
mesh_terms: D000818:Animals; D005260:Female; D007371:Interferon-gamma / Q000097:blood; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000235:genetics* / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D008198:Lymph Nodes / Q000469:parasitology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012727:Sex Characteristics; D012867:Skin / Q000473:pathology; D013154:Spleen / Q000469:parasitology
chemical_list: D007371:Interferon-gamma
references.citation: Eur J Immunol. 2003 May;33(5):1224-34
references.pmid: 12731047
references.citation: Genetics. 1989 Jan;121(1):185-99
references.pmid: 2563713
references.citation: Immunity. 1997 May;6(5):551-7
references.pmid: 9175833
references.citation: J Immunol. 1985 Nov;135(5):3505-11
references.pmid: 3930606
references.citation: Mamm Genome. 2000 Aug;11(8):645-8
references.pmid: 10920233
references.citation: Microbes Infect. 2002 Nov;4(14):1409-15
references.pmid: 12475631
references.citation: Science. 1994 Sep 30;265(5181):2037-48
references.pmid: 8091226
references.citation: Genomics. 1997 May 15;42(1):11-5
references.pmid: 9177770
references.citation: Int Immunol. 1996 Oct;8(10):1569-75
references.pmid: 8921436
references.citation: Genetics. 2005 Feb;169(2):855-62
references.pmid: 15371360
references.citation: Infect Immun. 1998 Jan;66(1):161-8
references.pmid: 9423853
references.citation: J Immunol. 2005 May 15;174(10):6340-5
references.pmid: 15879134
references.citation: Infect Immun. 1988 Dec;56(12):3316-9
references.pmid: 3182082
references.citation: Nat Rev Immunol. 2002 Nov;2(11):845-58
references.pmid: 12415308
references.citation: J Exp Med. 2006 Jan 23;203(1):177-88
references.pmid: 16418399
references.citation: Mamm Genome. 1996 Jan;7(1):55-8
references.pmid: 8903730
references.citation: Genetics. 2003 Mar;163(3):1041-6
references.pmid: 12663542
references.citation: Nat Rev Genet. 2006 Apr;7(4):294-305
references.pmid: 16543933
references.citation: J Exp Med. 1998 Dec 21;188(12):2289-99
references.pmid: 9858515
references.citation: Genes Immun. 2001 Nov;2(7):388-97
references.pmid: 11704805
references.citation: Genes Immun. 2002 Jun;3(4):187-95
references.pmid: 12058253
references.citation: Infect Immun. 2004 Apr;72(4):2350-7
references.pmid: 15039360
references.citation: Genes Immun. 2006 Apr;7(3):220-33
references.pmid: 16511555
references.citation: Exp Parasitol. 1990 Oct;71(3):267-75
references.pmid: 2170165
references.citation: Genes Immun. 2005 Jun;6(4):290-7
references.pmid: 15815685
references.citation: Science. 1996 Nov 22;274(5291):1392-3
references.pmid: 8966604
references.citation: Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9919-23
references.pmid: 12114535
references.citation: Nature. 1997 Feb 20;385(6618):733-6
references.pmid: 9034191
references.citation: Immunogenetics. 2004 Nov;56(8):564-71
references.pmid: 15503007
references.citation: Eur J Immunol. 1999 Sep;29(9):3047-50
references.pmid: 10508279
references.citation: Nat Rev Genet. 2005 Apr;6(4):271-86
references.pmid: 15803197
references.citation: Infect Immun. 1994 Oct;62(10):4112-7
references.pmid: 7927664
references.citation: Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):11792-7
references.pmid: 9751744
references.citation: Am J Trop Med Hyg. 2003 Nov;69(5):481-3
references.pmid: 14695084
references.citation: Immunol Rev. 2004 Oct;201:206-24
references.pmid: 15361243
references.citation: Int J Parasitol. 2002 Feb;32(2):179-85
references.pmid: 11812495
references.citation: Clin Microbiol Rev. 2005 Apr;18(2):293-305
references.pmid: 15831826
references.citation: Genes Immun. 2000 Feb;1(3):200-6
references.pmid: 11196712
references.citation: Genes Immun. 2003 Jan;4(1):30-9
references.pmid: 12595899
references.citation: J Virol. 1995 Nov;69(11):6958-64
references.pmid: 7474114
references.citation: J Exp Med. 1996 Apr 1;183(4):1501-14
references.pmid: 8666908
references.citation: J Natl Cancer Inst. 2001 Oct 3;93(19):1484-91
references.pmid: 11584065
references.citation: Infect Immun. 2003 Apr;71(4):2041-6
references.pmid: 12654824
references.citation: J Exp Med. 2004 Dec 20;200(12):1605-12
references.pmid: 15596523
references.citation: J Virol. 2003 Nov;77(21):11661-73
references.pmid: 14557652
references.citation: Mamm Genome. 1999 Jul;10(7):670-4
references.pmid: 10384038
references.citation: Science. 2007 Nov 2;318(5851):812-4
references.pmid: 17975068
references.citation: J Exp Med. 1997 May 5;185(9):1705-10
references.pmid: 9151907
references.citation: Immunogenetics. 2002 Jun;54(3):174-83
references.pmid: 12073146