Regulation of type 2 diabetes by helminth-induced Th2 immune response.
Helminth-induced type 2 cytokines increase the number of regulatory T cells and alternatively activated macrophages, resulting in modulation of the host-immune system. Studies on these parasite-induced immunoregulatory mechanisms might contribute to the development of new therapies for inflammatory diseases, including type 2 diabetes (T2D). Previous studies have suggested that progression of obesity-associated metabolic abnormalities is under pathophysiological control of CD4+ T cells. Glucose absorption through the intestinal epithelium reduced after infection in a STAT-6-dependent manner. In this study, we investigated whether infection with the gastrointestinal nematode parasite Heligmosomoides polygyrus (Hp) can modulate T2D-associated pathology in a mouse model (KK-Ay/TaJcl). KK-Ay/TaJcl mice were inoculated with infective third-stage Hp larvae and studied at Day 8 following infection. Uninfected KK-Ay/TaJcl mice showed high blood glucose levels even 120 min after administration of glucose by IP injection. However, it was significantly improved in the infected group. HOMA-IR, fat accumulation and FAS gene expression in the liver were significantly decreased by Hp infection. GLUT2 gene expression in this group was significantly lower than that in the uninfected diabetic mice, which might be related to the decrease in glucose absorption in the parasite-infected intestine. In conclusion, helminth-induced type 2 immune responses might contribute to T2D disease control.
School of Food, Agricultural, and Environmental Sciences, Miyagi University, Sendai City, Miyagi 982-0215, Japan.
Motoko
M
Morimoto
Noritsugu
N
Azuma
Hikaru
H
Kadowaki
Tatsuya
T
Abe
Yoshiko
Y
Suto
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology / Q000517:prevention & control*; D005786:Gene Expression Regulation; D005951:Glucose Tolerance Test; D051273:Glucose Transporter Type 2 / Q000235:genetics; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D009351:Nematospiroides dubius / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D001786:Blood Glucose; D016207:Cytokines; D051273:Glucose Transporter Type 2
J Clin Invest. 2013 Jan;123(1):261-71
23257358
Nat Med. 2006 Aug;12(8):955-60
16892038
Methods. 2001 Dec;25(4):386-401
11846608
Islets. 2010 Mar-Apr;2(2):130-2
21099307
J Mol Med (Berl). 2010 Jan;88(1):27-38
19844667
J Immunol. 2004 May 1;172(9):5616-21
15100305
Int Immunol. 2003 Jan;15(1):59-69
12502726
Exp Parasitol. 2012 Sep;132(1):76-89
21875581
J Physiol. 2007 Jul 1;582(Pt 1):379-92
17495045
Lipids Health Dis. 2011 Jul 21;10:120
21774832
J Immunol. 2007 Apr 1;178(7):4557-66
17372014
Curr Pharm Des. 2008;14(12):1225-30
18473870
Trends Immunol. 2012 Apr;33(4):181-9
22398370
Cardiovasc Diabetol. 2010 Oct 18;9:64
20955583
Immunity. 2015 Nov 17;43(5):998-1010
26522986
Cell Metab. 2008 Jun;7(6):496-507
18522831
Nat Clin Pract Endocrinol Metab. 2006 Jun;2(6):335-48
16932311
Metabolism. 1992 Dec;41(12):1373-8
1461145
PLoS One. 2014 Jan 23;9(1):e84763
24465430
Gastroenterology. 2005 Apr;128(4):825-32
15825065
N Engl J Med. 1988 Sep 29;319(13):829-34
3045553
Am J Clin Nutr. 1998 Mar;67(3 Suppl):577S-582S
9497173
Nat Rev Endocrinol. 2012 Dec;8(12):709-16
22847239
Diabetes. 2005 Oct;54(10):2939-45
16186396
J Physiol. 2003 Nov 1;552(Pt 3):823-32
12937289
J Immunol. 2006 Jan 1;176(1):491-5
16365442
J Autoimmun. 1988 Aug;1(4):309-17
3150923
Lipids. 2010 Dec;45(12):1109-16
20960069
Diabetes. 2009 Nov;58(11):2525-35
19690064
Gut. 2005 Jan;54(1):87-90
15591509
Infect Immun. 2009 Dec;77(12):5347-58
19752032
J Physiol. 2007 Apr 15;580(Pt. 2):593-604
17272350
Parasite Immunol. 1999 Apr;21(4):169-76
10320614
J Intern Med. 2007 Jan;261(1):32-43
17222166
J Immunol. 2006 Aug 1;177(3):1628-35
16849471
Cytokine. 2002 Jun 21;18(6):334-9
12160522
Science. 2011 Apr 8;332(6026):243-7
21436399
J Immunol. 2004 Feb 15;172(4):2424-30
14764713
Nat Med. 2009 Aug;15(8):921-9
19633657
J Biol Chem. 1957 May;226(1):497-509
13428781
Arthritis Res Ther. 2009;11(5):246
19849823
Cell Metab. 2008 Jun;7(6):485-95
18522830
Curr Opin Clin Nutr Metab Care. 2003 Mar;6(2):165-76
12589186
Nature. 2007 Jun 28;447(7148):1116-20
17515919
FASEB J. 2005 Jul;19(9):1108-19
15985534
Nat Rev Immunol. 2003 Jan;3(1):23-35
12511873
JAMA. 1994 May 11;271(18):1421-8
7848401
Inflamm Bowel Dis. 2012 Aug;18(8):1447-55
22223533
Parasite Immunol. 2015 Apr;37(4):171-9
25545318
Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5513-7
2062833
Diabetologia. 1985 Jul;28(7):412-9
3899825
Gastroenterology. 2008 Jul;135(1):217-225.e1
18471439