Th17 Cells Are More Protective Than Th1 Cells Against the Intracellular Parasite Trypanosoma cruzi.
Th17 cells are a subset of CD4+ T cells known to play a central role in the pathogenesis of many autoimmune diseases, as well as in the defense against some extracellular bacteria and fungi. However, Th17 cells are not believed to have a significant function against intracellular infections. In contrast to this paradigm, we have discovered that Th17 cells provide robust protection against Trypanosoma cruzi, the intracellular protozoan parasite that causes Chagas disease. Th17 cells confer significantly stronger protection against T. cruzi-related mortality than even Th1 cells, traditionally thought to be the CD4+ T cell subset most important for immunity to T. cruzi and other intracellular microorganisms. Mechanistically, Th17 cells can directly protect infected cells through the IL-17A-dependent induction of NADPH oxidase, involved in the phagocyte respiratory burst response, and provide indirect help through IL-21-dependent activation of CD8+ T cells. The discovery of these novel Th17 cell-mediated direct protective and indirect helper effects important for intracellular immunity highlights the diversity of Th17 cell roles, and increases understanding of protective T. cruzi immunity, aiding the development of therapeutics and vaccines for Chagas disease.
Department of Molecular Microbiology & Immunology, Saint Louis University School of Medicine, St. Louis, Missouri, USA.
Catherine W
CW
Cai
Department of Molecular Microbiology & Immunology, Saint Louis University School of Medicine, St. Louis, Missouri, USA.
Jennifer R
JR
Blase
Division of Infectious Diseases, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, Missouri, USA.
Xiuli
X
Zhang
Division of Infectious Diseases, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, Missouri, USA.
Christopher S
CS
Eickhoff
Department of Molecular Microbiology & Immunology, Saint Louis University School of Medicine, St. Louis, Missouri, USA.|Division of Infectious Diseases, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, Missouri, USA.
Daniel F
DF
Hoft
D019264:Adoptive Transfer; D000818:Animals; D014355:Chagas Disease / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005434:Flow Cytometry; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D016052:Protozoan Vaccines / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D014349:Trypanosoma cruzi
D016052:Protozoan Vaccines
J Immunol. 2013 Apr 15;190(8):3977-84
23479229
Infect Immun. 2006 Oct;74(10):5549-60
16988230
Immunity. 2009 May;30(5):646-55
19464987
J Immunol. 2011 Sep 1;187(5):2278-90
21775683
Infect Immun. 2005 Aug;73(8):4934-40
16041007
An Acad Bras Cienc. 2006 Mar;78(1):87-111
16532210
Immunol Rev. 2013 Mar;252(1):89-103
23405897
J Clin Invest. 2011 Dec;121(12):4787-95
22045567
Lancet. 2010 Apr 17;375(9723):1388-402
20399979
J Exp Med. 2005 Jan 3;201(1):139-48
15630141
Annu Rev Microbiol. 1993;47:385-411
8257103
Infect Immun. 2002 Dec;70(12):6715-25
12438346
J Immunol. 1998 Dec 1;161(11):6383-9
9834129
Methods Mol Biol. 1991;7:109-28
21416352
Annu Rev Immunol. 2009;27:485-517
19132915
Nat Immunol. 2013 May;14(5):514-22
23563688
J Immunol. 2010 Jul 15;185(2):1150-7
20562260
Am J Physiol Cell Physiol. 2001 Mar;280(3):C441-50
11171562
Infect Immun. 2000 Jan;68(1):197-204
10603388
J Leukoc Biol. 2003 Feb;73(2):209-12
12554797
FASEB J. 2010 Apr;24(4):1023-34
19940258
PLoS Pathog. 2009 Dec;5(12):e1000703
20041174
Hum Gene Ther. 2006 Sep;17(9):898-908
16972758
Hepatology. 1997 Feb;25(2):470-7
9021966
Eur J Immunol. 2011 Apr;41(4):936-51
21381020
J Immunol Methods. 1995 Sep 11;185(1):133-40
7665895
J Immunol. 1997 Dec 15;159(12):6120-30
9550413
Allergol Int. 2008 Jun;57(2):115-20
18427164
J Immunol. 2009 Aug 15;183(4):2337-48
19635915
Immunobiology. 2013 Jun;218(6):910-23
23182712
Nat Med. 2008 Mar;14(3):275-81
18264110
Am J Respir Crit Care Med. 2013 Nov 1;188(9):1137-46
24047412
Mol Microbiol. 2011 May;80(3):580-3
21375590
J Exp Med. 2009 Feb 16;206(2):299-311
19204111
Infect Immun. 2001 Sep;69(9):5477-86
11500420
J Immunol. 2007 Nov 15;179(10):6889-900
17982080
PLoS Negl Trop Dis. 2010 Feb 16;4(2):e604
20169058
Immunity. 2009 Jan 16;30(1):108-19
19144317
PLoS Pathog. 2012;8(4):e1002658
22577359
Curr Opin HIV AIDS. 2010 Mar;5(2):179-83
20543597
J Immunol. 2010 Sep 1;185(5):3103-10
20693426
Nature. 2012 Apr 26;484(7395):514-8
22466287
Exp Biol Med (Maywood). 2013 Apr;238(4):400-9
23760006
Arthritis Res Ther. 2013 Sep 26;15(5):R136
24286492
Arthritis Rheum. 2010 Oct;62(10):2876-85
20583102