title: Complement Activation by Giardia duodenalis Parasites through the Lectin Pathway Contributes to Mast Cell Responses and Parasite Control.
abstract: Infection with Giardia duodenalis is one of the most common causes of diarrheal disease in the world. While numerous studies have identified important contributions of adaptive immune responses to parasite control, much less work has examined innate immunity and its connections to the adaptive response during this infection. We explored the role of complement in immunity to Giardia using mice deficient in mannose-binding lectin (Mbl2) or complement factor 3a receptor (C3aR). Both strains exhibited delayed clearance of parasites and a reduced ability to recruit mast cells in the intestinal submucosa. C3aR-deficient mice had normal production of antiparasite IgA, butex vivo T cell recall responses were impaired. These data suggest that complement is a key factor in the innate recognition of Giardia and that recruitment of mast cells and activation of T cell immunity through C3a are important for parasite control.
authors.affiliation: Department of Biology, Georgetown University, Washington, DC, USA.
authors.forename: Erqiu
authors.initials: E
authors.lastname: Li
authors.affiliation: Department of Biology, Georgetown University, Washington, DC, USA.
authors.forename: Ernest A
authors.initials: EA
authors.lastname: Tako
authors.affiliation: Department of Biology, Georgetown University, Washington, DC, USA steven.singer@georgetown.edu.
authors.forename: Steven M
authors.identifier: http://orcid.org/0000-0001-5719-7535
authors.initials: SM
authors.lastname: Singer
mesh_terms: D000818:Animals; D037582:Complement Pathway, Mannose-Binding Lectin / Q000502:physiology*; D016829:Giardia lamblia / Q000502:physiology*; D005873:Giardiasis / Q000276:immunology*; D007070:Immunoglobulin A / Q000378:metabolism; D037601:Mannose-Binding Lectin / Q000235:genetics / Q000378:metabolism; D008407:Mast Cells / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D040081:Protein Array Analysis; D011951:Receptors, Complement / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000502:physiology
chemical_list: D007070:Immunoglobulin A; D037601:Mannose-Binding Lectin; C445639:Mbl2 protein, mouse; D011951:Receptors, Complement; D011994:Recombinant Proteins; C085567:complement C3a receptor
references.citation: J Immunol. 2006 Jan 1;176(1):516-21
references.pmid: 16365445
references.citation: Mucosal Immunol. 2016 May;9(3):767-76
references.pmid: 26442658
references.citation: J Exp Med. 2006 May 15;203(5):1371-81
references.pmid: 16651386
references.citation: Clin Infect Dis. 2006 Aug 1;43(3):289-94
references.pmid: 16804841
references.citation: J Immunol. 2007 Apr 15;178(8):5116-23
references.pmid: 17404294
references.citation: J Immunol. 2011 Oct 1;187(7):3769-75
references.pmid: 21873528
references.citation: Am J Trop Med Hyg. 2012 Feb;86(2):229-32
references.pmid: 22302853
references.citation: PLoS One. 2012;7(11):e47835
references.pmid: 23139754
references.citation: J Crohns Colitis. 2013 Mar;7(2):134-41
references.pmid: 22504031
references.citation: Infect Immun. 2007 Sep;75(9):4514-8
references.pmid: 17620354
references.citation: Eukaryot Cell. 2008 Nov;7(11):1930-40
references.pmid: 18820077
references.citation: Biochem Soc Trans. 2008 Dec;36(Pt 6):1461-6
references.pmid: 19021576
references.citation: Infect Immun. 2009 Feb;77(2):685-93
references.pmid: 19047410
references.citation: Am J Gastroenterol. 2009 Oct;104(10):2508-16
references.pmid: 19532127
references.citation: J Infect Dis. 2009 Nov 15;200(10):1540-7
references.pmid: 19827946
references.citation: PLoS One. 2010;5(3):e9721
references.pmid: 20300530
references.citation: Biochem Biophys Res Commun. 2010 May 7;395(3):382-6
references.pmid: 20382117
references.citation: Exp Parasitol. 2010 Nov;126(3):292-7
references.pmid: 20599999
references.citation: Nat Immunol. 2010 Oct;11(10):928-35
references.pmid: 20802484
references.citation: Virology. 2011 Mar 30;412(1):101-9
references.pmid: 21269656
references.citation: Clin Immunol. 2011 Jul;140(1):63-70
references.pmid: 21489885
references.citation: Scand J Gastroenterol. 2011 Oct;46(10):1275-8
references.pmid: 21702710
references.citation: Infect Immun. 2000 Jan;68(1):170-5
references.pmid: 10603384
references.citation: J Immunol. 2000 Feb 1;164(3):1478-87
references.pmid: 10640765
references.citation: J Infect Dis. 2000 Apr;181(4):1510-2
references.pmid: 10751141
references.citation: Gastroenterology. 2000 Nov;119(5):1236-42
references.pmid: 11054381
references.citation: Clin Microbiol Rev. 2001 Jul;14(3):447-75
references.pmid: 11432808
references.citation: Genes Immun. 2001 Oct;2(6):323-8
references.pmid: 11607788
references.citation: Parasitol Res. 2002 Feb;88(2):113-7
references.pmid: 11936498
references.citation: J Immunol. 2002 Dec 15;169(12):6945-50
references.pmid: 12471128
references.citation: Infect Immun. 2003 Mar;71(3):1566-8
references.pmid: 12595478
references.citation: Parasite Immunol. 2003 May;25(5):259-70
references.pmid: 12969444
references.citation: J Trop Pediatr. 2004 Apr;50(2):90-3
references.pmid: 15088797
references.citation: Infect Immun. 2004 Nov;72(11):6642-9
references.pmid: 15501797
references.citation: Aust J Exp Biol Med Sci. 1983 Oct;61 ( Pt 5):599-615
references.pmid: 6689264
references.citation: J Immunol. 1984 Apr;132(4):2046-52
references.pmid: 6699407
references.citation: J Cell Biochem. 1983;23(1-4):47-56
references.pmid: 6676355
references.citation: J Exp Med. 1987 Jun 1;165(6):1743-8
references.pmid: 2953846
references.citation: J Exp Med. 1988 Jan 1;167(1):73-88
references.pmid: 3335831
references.citation: J Infect Dis. 1988 Jun;157(6):1257-60
references.pmid: 3373026
references.citation: Clin Exp Immunol. 1992 Feb;87(2):304-9
references.pmid: 1735194
references.citation: Epidemiol Infect. 1992 Aug;109(1):1-22
references.pmid: 1499664
references.citation: J Leukoc Biol. 1992 Oct;52(4):369-76
references.pmid: 1402387
references.citation: Adv Parasitol. 1993;32:71-160
references.pmid: 8237618
references.citation: Infect Immun. 1994 Aug;62(8):3583-5
references.pmid: 8039934
references.citation: Infect Immun. 1996 Jul;64(7):2649-56
references.pmid: 8698491
references.citation: J Pediatr Gastroenterol Nutr. 1997 Jan;24(1):79-88
references.pmid: 9093992
references.citation: J Parasitol. 1997 Oct;83(5):908-12
references.pmid: 9379297
references.citation: Scand J Immunol. 1997 Aug;46(2):204-8
references.pmid: 9584002
references.citation: J Infect Dis. 1998 Oct;178(4):1221-4
references.pmid: 9806066
references.citation: J Virol. 2005 Jun;79(12):7466-77
references.pmid: 15919902
references.citation: Infect Immun. 2005 Dec;73(12):8204-8
references.pmid: 16299316
references.citation: MBio. 2013;4(6):e00660-13
references.pmid: 24194537
references.citation: Vet Parasitol. 2014 May 28;202(3-4):145-55
references.pmid: 24702771
references.citation: Infect Immun. 2014 Aug;82(8):3333-40
references.pmid: 24866800
references.citation: Parasite. 2014;21:55
references.pmid: 25347704
references.citation: Parasite Immunol. 2014 Dec;36(12):627-46
references.pmid: 24871487
references.citation: Microbes Infect. 2015 Jun;17(6):462-7
references.pmid: 25797399
references.citation: Exp Parasitol. 2015 Sep;156:68-78
references.pmid: 26071205
references.citation: Mucosal Immunol. 2015 Nov;8(6):1275-84
references.pmid: 25736459
references.citation: Clin Vaccine Immunol. 2016 Jan;23(1):11-8
references.pmid: 26376930
references.citation: PLoS Negl Trop Dis. 2016 Jan;10(1):e0004257
references.pmid: 26745156
references.citation: Infect Immun. 2006 Apr;74(4):2473-6
references.pmid: 16552082