- INTRODUCTION
- METAINFLAMMATION, -INSULIN RESISTANCE (IR), TYPE-2 DIABETES (T2DM)
- IMMUNOMODULATION BY HELMINTHS
- CROSS TALK BETWEEN INNATE AND ADAPTIVE IMMUNE CELLS
- ROLE OF INNATE IMMUNE CELLS IN IR AND IMMUNOMODULATION
- Macrophages in IR and immunomodulation.
- DC in IR and immunomodulation.
- NK cells in IR and immunomodulation.
- Neutrophils in IR and immunomodulation.
- Eosinophils in IR and immunomodulation.
- Basophils and mast cells in IR and immunomodulation.
- Myeloid-derived supressor cells (MDSCs) in IR and immunomodulation.
- Innate lymphoid cells (ILCs) in IR and immunomodulation.
- ADAPTIVE IMMUNE CELLS IN IR AND IMMUNOMODULATION
- CONCLUSION
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Astrup A, Finer N, 2000. Redefining type 2 diabetes: ‘diabesity’ or ‘obesity dependent diabetes mellitus’? Obes Rev 1: 57–59.
-
2.
Hotamisligil GS, 2006. Inflammation and metabolic disorders. Nature 444: 860–867.
-
3.
Lumeng CN, Saltiel AR, 2011. Inflammatory links between obesity and metabolic disease. J Clin Invest 121: 2111–2117.
-
4.
Aravindhan V, Madhumitha H, 2016. Metainflammation in diabetic coronary artery disease: emerging role of innate and adaptive immune responses. J Diabetes Res 2016: 6264149.
-
5.
Ding H, Triggle CR, 2005. Endothelial cell dysfunction and the vascular complications associated with type 2 diabetes: assessing the health of the endothelium. Vasc Health Risk Manag 1: 55–71.
-
6.
Kendall DM, Harmel AP, 2002. The metabolic syndrome, type 2 diabetes, and cardiovascular disease: understanding the role of insulin resistance. Am J Manag Care 8: S635–S653; quiz S654–S657.
-
7.
Pedersen O, 1999. Genetics of insulin resistance. Exp Clin Endocrinol Diabetes 107: 113–118.
-
8.
Reaven GM, 1988. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 37: 1595–1607.
-
9.
Hong Y, Pedersen NL, Brismar K, de Faire U, 1997. Genetic and environmental architecture of the features of the insulin-resistance syndrome. Am J Hum Genet 60: 143–152.
-
10.
Bell DS, 2000. Inflammation, insulin resistance, infection, diabetes, and atherosclerosis. Endocr Pract 6: 272–276.
-
11.
Liu Q, Sundar K, Mishra PK, Mousavi G, Liu Z, Gaydo A, Alem F, Lagunoff D, Bleich D, Gause WC, 2009. Helminth infection can reduce insulitis and type 1 diabetes through CD25- and IL-10-independent mechanisms. Infect Immun 77: 5347–5358.
-
12.
Hübner MP et al. 2012. Helminth protection against autoimmune diabetes in nonobese diabetic mice is independent of a type 2 immune shift and requires TGF-β. J Immunol 188: 559–568.
-
13.
Hübner MP, Stocker JT, Mitre E, 2009. Inhibition of type 1 diabetes in filaria-infected non-obese diabetic mice is associated with a T helper type 2 shift and induction of FoxP3+ regulatory T cells. Immunology 127: 512–522.
-
14.
Hussaarts L et al. 2015. Chronic helminth infection and helminth-derived egg antigens promote adipose tissue M2 macrophages and improve insulin sensitivity in obese mice. FASEB J 29: 3027–3039.
-
15.
Berbudi A et al. 2016. Filarial infection or antigen administration improves glucose tolerance in diet-induced obese mice. J Innate Immun 8: 601–616.
-
16.
Yang Z et al. 2013. Parasitic nematode-induced modulation of body weight and associated metabolic dysfunction in mouse models of obesity. Infect Immun 81: 1905–1914.
-
17.
Aravindhan V, Mohan V, Surendar J, Rao MM, Ranjani H, Kumaraswami V, Nutman TB, Babu S, 2010. Decreased prevalence of lymphatic filariasis among subjects with type-1 diabetes. Am J Trop Med Hyg 83: 1336–1339.
-
18.
Aravindhan V, Mohan V, Surendar J, Muralidhara Rao M, Pavankumar N, Deepa M, Rajagopalan R, Kumaraswami V, Nutman TB, Babu S, 2010. Decreased prevalence of lymphatic filariasis among diabetic subjects associated with a diminished pro-inflammatory cytokine response (CURES 83). PLoS Negl Trop Dis 4: e707.
-
19.
Aravindhan V, Mohan V, Surendar J, Rao MM, Anuradha R, Deepa M, Babu S, 2012. Effect of filarial infection on serum inflammatory and atherogenic biomarkers in coronary artery disease (CURES-121). Am J Trop Med Hyg 86: 828–833.
-
20.
Wiria AE et al. 2015. Infection with soil-transmitted helminths is associated with increased insulin sensitivity. PLoS One 10: e0127746.
-
21.
Hewitson JP, Grainger JR, Maizels RM, 2009. Helminth immunoregulation: the role of parasite secreted proteins in modulating host immunity. Mol Biochem Parasitol 167: 1–11.
-
22.
Venugopal PG, Nutman TB, Semnani RT, 2009. Activation and regulation of toll-like receptors (TLRs) by helminth parasites. Immunol Res 43: 252–263. Erratum in: PLoS One 2015;10(8).
-
23.
Tahapary DL et al. 2017. Effect of anthelmintic treatment on insulin resistance: a cluster-randomized placebo-controlled trial in Indonesia. Clin Infect Dis 65: 764–771.
-
24.
Crowe J, Lumb FE, Harnett MM, Harnett W, 2017. Parasite excretory-secretory products and their effects on metabolic syndrome. Parasite Immunol 39(5).
-
25.
Shanker A, Thounaojam MC, Mishra MK, Dikov MM, Uzhachenko RV, 2015. Innate-adaptive immune crosstalk. J Immunol Res 2015: 982465.
-
26.
Cheroutre H, Huang Y, 2013. Crosstalk between adaptive and innate immune cells leads to high quality immune protection at the mucosal borders. Adv Exp Med Biol 785: 43–47.
-
27.
Kambayashi T, Laufer TM, 2014. Atypical MHC class II-expressing antigen-presenting cells: can anything replace a dendritic cell? Nat Rev Immunol 14: 719–730.
-
28.
Tsuji T, 1976. Subcutaneous fat necrosis of the newborn: light and electron microscopic studies. Br J Dermatol 95: 407–416.
-
29.
Xu H et al. 2003. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112: 1821–1830.
-
30.
Murray PJ et al. 2014. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 41: 14–20.
-
31.
Amano SU, Cohen JL, Vangala P, Tencerova M, Nicoloro SM, Yawe JC, Shen Y, Czech MP, Aouadi M, 2014. Local proliferation of macrophages contributes to obesity-associated adipose tissue inflammation. Cell Metab 19: 162–171.
-
32.
Fujisaka S et al. 2009. Regulatory mechanisms for adipose tissue M1 and M2 macrophages in diet-induced obese mice. Diabetes 58: 2574–2582.
-
33.
Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr, 2003. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112: 1796–1808.
-
34.
Lumeng CN, DelProposto JB, Westcott DJ, Saltiel AR, 2008. Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes 57: 3239–3246.
-
35.
Sun K, Kusminski CM, Scherer PE, 2011. Adipose tissue remodeling and obesity. J Clin Invest 121: 2094–2101.
-
36.
Suganami T, Ogawa Y, 2010. Adipose tissue macrophages: their role in adipose tissue remodeling. J Leukoc Biol 88: 33–39.
-
37.
Heilbronn LK, Campbell LV, 2008. Adipose tissue macrophages, low grade inflammation and insulin resistance in human obesity. Curr Pharm Des 14: 1225–1230.
-
38.
Lumeng CN, Bodzin JL, Saltiel AR, 2007. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 117: 175–184.
-
39.
Weisberg SP, Hunter D, Huber R, Lemieux J, Slaymaker S, Vaddi K, Charo I, Leibel RL, Ferrante AW Jr, 2006. CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J Clin Invest 116: 115–124.
-
40.
Patsouris D, Li PP, Thapar D, Chapman J, Olefsky JM, Neels JG, 2008. Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals. Cell Metab 8: 301–309.
-
41.
Herbert DR et al. 2004. Alternative macrophage activation is essential for survival during schistosomiasis and downmodulates T helper 1 responses and immunopathology. Immunity 20: 623–635.
-
42.
Nair MG, Cochrane DW, Allen JE, 2003. Macrophages in chronic type 2 inflammation have a novel phenotype characterized by the abundant expression of Ym1 and Fizz1 that can be partly replicated in vitro. Immunol Lett 85: 173–180.
-
43.
Noel W, Raes G, Hassanzadeh Ghassabeh G, De Baetselier P, Beschin A, 2004. Alternatively activated macrophages during parasite infections. Trends Parasitol 20: 126–133.
-
44.
Loke P, Gallagher I, Nair MG, Zang X, Brombacher F, Mohrs M, Allison JP, Allen JE, 2007. Alternative activation is an innate response to injury that requires CD4+ T cells to be sustained during chronic infection. J Immunol 179: 3926–3936.
-
45.
Reyes JL, Terrazas LI, 2007. The divergent roles of alternatively activated macrophages in helminthic infections. Parasite Immunol 29: 609–619.
-
46.
Maizels RM, Yazdanbakhsh M, 2003. Immune regulation by helminth parasites: cellular and molecular mechanisms. Nat Rev Immunol 3: 733–744.
-
47.
Stefanovic-Racic M et al. 2012. Dendritic cells promote macrophage infiltration and comprise a substantial proportion of obesity-associated increases in CD11c+ cells in adipose tissue and liver. Diabetes 61: 2330–2339.
-
48.
Stefanovic-Racic M et al. 2012. Dendritic cells promote macrophage infiltration and comprise a substantial proportion of obesity-associated increases in CD11c+ cells in adipose tissue and liver. Diabetes 61: 2330–2339.
-
49.
Bertola A et al. 2012. Identification of adipose tissue dendritic cells correlated with obesity-associated insulin-resistance and inducing Th17 responses in mice and patients. Diabetes 61: 2238–2247.
-
50.
Terrazas CA, Terrazas LI, Gomez-Garcia L, 2010. Modulation of dendritic cell responses by parasites: a common strategy to survive. J Biomed Biotechnol 2010: 357106.
-
51.
Kane CM, Jung E, Pearce EJ, 2008. Schistosoma mansoni egg antigen-mediated modulation of Toll-like receptor (TLR)-induced activation occurs independently of TLR2, TLR4, and MyD88. Infect Immun 76: 5754–5759.
-
52.
Goodridge HS, Marshall FA, Else KJ, Houston KM, Egan C, Al-Riyami L, Liew FY, Harnett W, Harnett MM, 2005. Immunomodulation via novel use of TLR4 by the filarial nematode phosphorylcholine-containing secreted product, ES-62. J Immunol 174: 284–293.
-
53.
Terrazas CA, Terrazas LI, Gomez-Garcia L, 2010. Modulation of dendritic cell responses by parasites: a common strategy to survive. J Biomed Biotechnol 2010: 357106.
-
54.
Vannella KM et al. 2016. Combinatorial targeting of TSLP, IL-25, and IL-33 in type 2 cytokine-driven inflammation and fibrosis. Sci Transl Med 8: 337ra65.
-
55.
Anand G, Vasanthakumar R, Mohan V, Babu S, Aravindhan V, 2015. Increased IL-12 and decreased IL-33 serum levels are associated with increased Th1 and suppressed Th2 cytokine profile in patients with diabetic nephropathy (CURES-134). Int J Clin Exp Pathol 7: 8008–8015.
-
56.
Nutman TB, 2015. Looking beyond the induction of Th2 responses to explain immunomodulation by helminths. Parasite Immunol 37: 304–313.
-
57.
Semnani RT, Liu AY, Sabzevari H, Kubofcik J, Zhou J, Gilden JK, Nutman TB, 2003. Brugia malayi microfilariae induce cell death in human dendritic cells, inhibit their ability to make IL-12 and IL-10, and reduce their capacity to activate CD4+ T cells. J Immunol 171: 1950–1960.
-
58.
Semnani RT, Venugopal PG, Leifer CA, Mostbock S, Sabzevari H, Nutman TB, 2008. Inhibition of TLR3 and TLR4 function and expression in human dendritic cells by helminth parasites. Blood 112: 1290–1298.
-
59.
O’Rourke RW, Metcalf MD, White AE, Madala A, Winters BR, Maizlin II, Jobe BA, Roberts CT Jr, Slifka MK, Marks DL, 2009. Depot-specific differences in inflammatory mediators and a role for NK cells and IFN-gamma in inflammation in human adipose tissue. Int J Obes 33: 978–990.
-
60.
Bonamichi BDSF, Lee J, 2017. Unusual suspects in the development of obesity-induced inflammation and insulin resistance: NK cells, iNKT cells, and ILCs. Diabetes Metab J 41: 229–250.
-
61.
Chung JJ, Markiewicz MA, Polic B, Shaw AS, 2014. Role of NKG2D in obesity-induced adipose tissue inflammation and insulin resistance. PLoS One 9: e110108.
-
62.
Babu S, Blauvelt CP, Nutman TB, 2007. Filarial parasites induce NK cell activation, type 1 and type 2 cytokine secretion, and subsequent apoptotic cell death. J Immunol 179: 2445–2456.
-
63.
Korten S, Volkmann L, Saeftel M, Fischer K, Taniguchi M, Fleischer B, Hoerauf A, 2002. Expansion of NK cells with reduction of their inhibitory Ly-49A, Ly-49C, and Ly-49G2 receptor-expressing subsets in a murine helminth infection: contribution to parasite control. J Immunol 168: 5199–5206.
-
64.
Mantovani A, Cassatella MA, Costantini C, Jaillon S, 2011. Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol 11: 519–531.
-
65.
Talukdar S et al. 2012. Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nat Med 18: 1407–1412.
-
66.
MacDonald AS, Araujo MI, Pearce EJ, 2002. Immunology of parasitic helminth infections. Infect Immun 70: 427–433.
-
67.
Tsuda Y, Takahashi H, Kobayashi M, Hanafusa T, Herndon DN, Suzuki F, 2004. Three different neutrophil subsets exhibited in mice with different susceptibilities to infection by methicillin-resistant Staphylococcus aureus. Immunity 21: 215–226.
-
68.
Anbu KA, Joshi P, 2008. Identification of a 55 kDa Haemonchus contortus excretory/secretory glycoprotein as a neutrophil inhibitory factor. Parasite Immunol 30: 23–30.
-
69.
Zang X, Atmadja AK, Gray P, Allen JE, Gray CA, Lawrence RA, Yazdanbakhsh M, Maizels RM, 2000. The serpin secreted by Brugia malayi microfilariae, Bm-SPN-2, elicits strong, but short-lived, immune responses in mice and humans. J Immunol 165: 5161–5169.
-
70.
Schroeder JH, Simbi BH, Ford L, Cole SR, Taylor MJ, Lawson C, Lawrence RA, 2012. Live Brugia malayi microfilariae inhibit transendothelial migration of neutrophils and monocytes. PLoS Negl Trop Dis 6: e1914.
-
71.
Seki T, Kumagai T, Kwansa-Bentum B, Furushima-Shimogawara R, Anyan WK, Miyazawa Y, Iwakura Y, Ohta N, 2011. Interleukin-4 (IL-4) and IL-13 suppress excessive neutrophil infiltration and hepatocyte damage during acute murine schistosomiasis japonica. Infect Immun 80: 159–168.
-
72.
Makepeace BL, Martin C, Turner JD, Specht S, 2012. Granulocytes in helminth infection–who is calling the shots? Curr Med Chem 19: 1567–1586.
-
73.
Matthaei KI, Foster P, Young IG, 1997. The role of interleukin-5 (IL-5) in vivo: studies with IL-5 deficient mice. Mem Inst Oswaldo Cruz 92 (Suppl 2): 63–68.
-
74.
Melo RC, Weller PF, 2010. Piecemeal degranulation in human eosinophils: a distinct secretion mechanism underlying inflammatory responses. Histol Histopathol 25: 1341–1354.
-
75.
Walsh GM, 2001. Eosinophil granule proteins and their role in disease. Curr Opin Hematol 8: 28–33.
-
76.
Wu D, Molofsky AB, Liang HE, Ricardo-Gonzalez RR, Jouihan HA, Bando JK, Chawla A, Locksley RM, 2011. Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science 332: 243–247.
-
77.
Pang J, Rhodes DH, Pini M, Akasheh RT, Castellanos KJ, Cabay RJ, Cooper D, Perretti M, Fantuzzi G, 2013. Increased adiposity, dysregulated glucose metabolism and systemic inflammation in galectin-3 KO mice. PLoS One 8: e57915.
-
78.
Baum LG, 2011. Burn control, an adipocyte-specific function for galectin-12. Proc Natl Acad Sci USA 108: 18575–18576.
-
79.
Molofsky AB, Nussbaum JC, Liang HE, Van Dyken SJ, Cheng LE, Mohapatra A, Chawla A, Locksley RM, 2013. Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages. J Exp Med 210: 535–549.
-
80.
Minton K, 2011. Granulocytes: a weighty role for eosinophils. Nat Rev Immunol 11: 299.
-
81.
Klion AD, Nutman TB, 2004. The role of eosinophils in host defense against helminth parasites. J Allergy Clin Immunol 113: 30–37.
-
82.
Shin MH, Lee YA, Min DY, 2009. Eosinophil-mediated tissue inflammatory responses in helminth infection. Korean J Parasitol 47 (Suppl): S125–S131.
-
83.
Meeusen EN, Balic A, 2000. Do eosinophils have a role in the killing of helminth parasites? Parasitol Today 16: 95–101.
-
84.
Fabre V, Beiting DP, Bliss SK, Gebreselassie NG, Gagliardo LF, Lee NA, Lee JJ, Appleton JA, 2009. Eosinophil deficiency compromises parasite survival in chronic nematode infection. J Immunol 182: 1577–1583.
-
85.
Gebreselassie NG, Moorhead AR, Fabre V, Gagliardo LF, Lee NA, Lee JJ, Appleton JA, 2012. Eosinophils preserve parasitic nematode larvae by regulating local immunity. J Immunol 188: 417–425.
-
86.
Sun S, Ji Y, Kersten S, Qi L, 2012. Mechanisms of inflammatory responses in obese adipose tissue. Annu Rev Nutr 32: 261–286.
-
87.
Siracusa MC, Comeau MR, Artis D, 2011. New insights into basophil biology: initiators, regulators, and effectors of type 2 inflammation. Ann N Y Acad Sci 1217: 166–177.
-
88.
Chirumbolo S, 2012. State-of-the-art review about basophil research in immunology and allergy: is the time right to treat these cells with the respect they deserve? Blood Transfus 10: 148–164.
-
89.
Zhang J, Shi GP, 2012. Mast cells and metabolic syndrome. Biochim Biophys Acta 1822: 14–20.
-
90.
Johnson AR, Milner JJ, Makowski L, 2012. The inflammation highway: metabolism accelerates inflammatory traffic in obesity. Immunol Rev 249: 218–238.
-
91.
Altintas MM, Azad A, Nayer B, Contreras G, Zaias J, Faul C, Reiser J, Nayer A, 2011. Mast cells, macrophages, and crown-like structures distinguish subcutaneous from visceral fat in mice. J Lipid Res 52: 480–488.
-
92.
Liu J et al. 2009. Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice. Nat Med 15: 940–945.
-
93.
Shi MA, Shi GP, 2012. Different roles of mast cells in obesity and diabetes: lessons from experimental animals and humans. Front Immunol 3: 7.
-
94.
Xu JM, Shi GP, 2012. Emerging role of mast cells and macrophages in cardiovascular and metabolic diseases. Endocr Rev 33: 71–108.
-
95.
Bell RG, 1996. IgE, allergies and helminth parasites: a new perspective on an old conundrum. Immunol Cell Biol 74: 337–345.
-
96.
Mitre E, Nutman TB, 2006. Basophils, basophilia and helminth infections. Chem Immunol Allergy 90: 141–156.
-
97.
Voehringer D, 2009. The role of basophils in helminth infection. Trends Parasitol 25: 551–556.
-
98.
Ohnmacht C, Voehringer D, 2009. Basophil effector function and homeostasis during helminth infection. Blood 113: 2816–2825.
-
99.
Cadman ET, Lawrence RA, 2010. Granulocytes: effector cells or immunomodulators in the immune response to helminth infection? Parasite Immunol 32: 1–19.
-
100.
Voehringer D, 2011. Basophils in immune responses against helminths. Microbes Infect 13: 881–887.
-
101.
Leon-Cabrera S, Flisser A, 2012. Are basophils important mediators for helminth-induced Th2 immune responses? A debate. J Biomed Biotechnol 2012: 274150.
-
102.
Makki K, Froguel P, Wolowczuk I, 2013. Adipose tissue in obesity-related inflammation and insulin resistance: cells, cytokines, and chemokines. ISRN Inflamm 2013: 139239.
-
103.
Xia S, Sha H, Yang L, Ji Y, Ostrand-Rosenberg S, Qi L, 2011. Gr-1+ CD11b+ myeloid-derived suppressor cells suppress inflammation and promote insulin sensitivity in obesity. J Biol Chem 286: 23591–23599.
-
104.
Brys L, Beschin A, Raes G, Ghassabeh GH, Noel W, Brandt J, Brombacher F, De Baetselier P, 2005. Reactive oxygen species and 12/15-lipoxygenase contribute to the antiproliferative capacity of alternatively activated myeloid cells elicited during helminth infection. J Immunol 174: 6095–6104.
-
105.
Yang Q et al., 2017. A Schistosoma japonicum infection promotes the expansion of myeloid-derived suppressor cells by activating the JAK/STAT3 pathway. J Immunol 198: 4716–4727.
-
106.
Eberl G, Colonna M, Di Santo JP, McKenzie AN, 2015. Innate lymphoid cells. Innate lymphoid cells: a new paradigm in immunology. Science 348: aaa6566.
-
107.
Brestoff JR et al. 2015. Group 2 innate lymphoid cells promote beiging of white adipose tissue and limit obesity. Nature 519: 242–246.
-
108.
O’Sullivan TE, Rapp M, Fan X, Weizman OE, Bhardwaj P, Adams NM, Walzer T, Dannenberg AJ, Sun JC, 2016. Adipose-resident group 1 innate lymphoid cells promote obesity-associated insulin resistance. Immunity 45: 428–441.
-
109.
Neill DR et al. 2010. Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity. Nature 464: 1367–1370.
-
110.
Hams E, Bermingham R, Wurlod FA, Hogan AE, O’Shea D, Preston RJ, Rodewald HR, McKenzie AN, Fallon PG, 2015. The helminth T2 RNase omega1 promotes metabolic homeostasis in an IL-33- and group 2 innate lymphoid cell-dependent mechanism. FASEB J 30: 824–835.
-
111.
Lee MW, Odegaard JI, Mukundan L, Qiu Y, Molofsky AB, Nussbaum JC, Yun K, Locksley RM, Chawla A, 2014. Activated type 2 innate lymphoid cells regulate beige fat biogenesis. Cell 160: 74–87.
-
112.
Feuerer M et al. 2009. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med 15: 930–939.
-
113.
Cipolletta D, Feuerer M, Li A, Kamei N, Lee J, Shoelson SE, Benoist C, Mathis D, 2012. PPAR-gamma is a major driver of the accumulation and phenotype of adipose tissue Treg cells. Nature 486: 549–553.
-
114.
Winer DA et al. 2011. B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat Med 17: 610–617.
-
115.
Rocha VZ, Folco EJ, Sukhova G, Shimizu K, Gotsman I, Vernon AH, Libby P, 2008. Interferon-gamma, a Th1 cytokine, regulates fat inflammation: a role for adaptive immunity in obesity. Circ Res 103: 467–476.
-
116.
Stanya KJ et al. 2013. Direct control of hepatic glucose production by interleukin-13 in mice. J Clin Invest 123: 261–271.
-
117.
Harford KA, Reynolds CM, McGillicuddy FC, Roche HM, 2011. Fats, inflammation and insulin resistance: insights to the role of macrophage and T-cell accumulation in adipose tissue. Proc Nutr Soc 70: 408–417.
-
118.
Kang K, Reilly SM, Karabacak V, Gangl MR, Fitzgerald K, Hatano B, Lee CH, 2008. Adipocyte-derived Th2 cytokines and myeloid PPARdelta regulate macrophage polarization and insulin sensitivity. Cell Metab 7: 485–495.
-
119.
Winer S et al. 2009. Normalization of obesity-associated insulin resistance through immunotherapy. Nat Med 15: 921–929.
-
120.
Surendar J, Mohan V, Rao MM, Babu S, Aravindhan V, 2011. Increased levels of both Th1 and Th2 cytokines in subjects with metabolic syndrome (CURES-103). Diabetes Technol Ther 13: 477–482.
-
121.
Surendar J, Aravindhan V, Rao MM, Ganesan A, Mohan V, 2011. Decreased serum interleukin-17 and increased transforming growth factor-β levels in subjects with metabolic syndrome (Chennai Urban Rural Epidemiology Study-95). Metabolism 60: 586–590.
-
122.
Cipolletta D, Feuerer M, Li A, Kamei N, Lee J, Shoelson SE, Benoist C, Mathis D, 2012. PPAR-γ is a major driver of the accumulation and phenotype of adipose tissue Treg cells. Nature 486: 549–553.
-
123.
Hamaguchi M, Sakaguchi S, 2012. Regulatory T cells expressing PPAR-γ control inflammation in obesity. Cell Metab 16: 4–6.
-
124.
Eller K, Kirsch A, Wolf AM, Sopper S, Tagwerker A, Stanzl U, Wolf D, Patsch W, Rosenkranz AR, Eller P, 2011. Potential role of regulatory T cells in reversing obesity-linked insulin resistance and diabetic nephropathy. Diabetes 60: 2954–2962.
-
125.
Pearce EJ, M kane C, Sun J, J Taylor J, McKee AS, Cervi L, 2004. Th2 response polarization during infection with the helminth parasite Schistosoma mansoni. Immunol Rev 201: 117–126.
-
126.
Babu S, Bhat SQ, Pavan Kumar N, Lipira AB, Kumar S, Karthik C, Kumaraswami V, Nutman TB, 2009. Filarial lymphedema is characterized by antigen-specific Th1 and th17 proinflammatory responses and a lack of regulatory T cells. PLoS Negl Trop Dis 3: e420.
-
127.
Babu S, Kumaraswami V, Nutman TB, 2005. Transcriptional control of impaired Th1 responses in patent lymphatic filariasis by T-box expressed in T cells and suppressor of cytokine signaling genes. Infect Immun 73: 3394–3401.
-
128.
Babu S, Blauvelt CP, Kumaraswami V, Nutman TB, 2006. Regulatory networks induced by live parasites impair both Th1 and Th2 pathways in patent lymphatic filariasis: implications for parasite persistence. J Immunol 176: 3248–3256.
-
129.
King CL, Mahanty S, Kumaraswami V, Abrams JS, Regunathan J, Jayaraman K, Ottesen EA, Nutman TB, 1993. Cytokine control of parasite-specific anergy in human lymphatic filariasis. Preferential induction of a regulatory T helper type 2 lymphocyte subset. J Clin Invest 92: 1667–1673.
-
130.
Grainger JR et al. 2010. Helminth secretions induce de novo T cell Foxp3 expression and regulatory function through the TGF-β pathway. J Exp Med 207: 2331–2341.
-
131.
Harnett W, Deehan MR, Houston KM, Harnett MM, 1999. Immunomodulatory properties of a phosphorylcholine-containing secreted filarial glycoprotein. Parasite Immunol 21: 601–608.
-
132.
Marshall FA, Grierson AM, Garside P, Harnett W, Harnett MM, 2005. ES-62, an immunomodulator secreted by filarial nematodes, suppresses clonal expansion and modifies effector function of heterologous antigen-specific T cells in vivo. J Immunol 175: 5817–5826.
-
133.
Strissel KJ, DeFuria J, Shaul ME, Bennett G, Greenberg AS, Obin MS, 2010. T-cell recruitment and Th1 polarization in adipose tissue during diet-induced obesity in C57BL/6 mice. Obesity (Silver Spring) 18: 1918–1925.
-
134.
Kintscher U et al. 2008. T-lymphocyte infiltration in visceral adipose tissue: a primary event in adipose tissue inflammation and the development of obesity-mediated insulin resistance. Arterioscler Thromb Vasc Biol 28: 1304–1310.
-
135.
Nishimura S et al. 2009. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med 15: 914–920.
-
136.
Kalinkovich A, Weisman Z, Greenberg Z, Nahmias J, Eitan S, Stein M, Bentwich Z, 1998. Decreased CD4 and increased CD8 counts with T cell activation is associated with chronic helminth infection. Clin Exp Immunol 114: 414–421.
-
137.
Borkow G, Bentwich Z, 2004. Chronic immune activation associated with chronic helminthic and human immunodeficiency virus infections: role of hyporesponsiveness and anergy. Clin Microbiol Rev 17: 1012–1030 (table of contents).
-
138.
Hartmann W, Brenz Y, Kingsley MT, Ajonina-Ekoti I, Brattig NW, Liebau E, Breloer M, 2013. Nematode-derived proteins suppress proliferation and cytokine production of antigen-specific T cells via induction of cell death. PLoS One 8: e68380.
-
139.
Anthony RM, Rutitzky LI, Urban JF Jr, Stadecker MJ, Gause WC, 2007. Protective immune mechanisms in helminth infection. Nat Rev Immunol 7: 975–987.
-
140.
Wang YM, Alexander SI, 2009. CD8 regulatory T cells: what’s old is now new. Immunol Cell Biol 87: 192–193.
-
141.
Kolbaum J, Tartz S, Hartmann W, Helm S, Nagel A, Heussler V, Sebo P, Fleischer B, Jacobs T, Breloer M, 2011. Nematode-induced interference with the anti-Plasmodium CD8+ T-cell response can be overcome by optimizing antigen administration. Eur J Immunol 42: 890–900.
-
142.
Osborne LC et al. 2014. Coinfection. Virus-helminth coinfection reveals a microbiota-independent mechanism of immunomodulation. Science 345: 578–582.
-
143.
Buerfent BC, Gondorf F, Wohlleber D, Schumak B, Hoerauf A, Hubner MP, 2014. Escherichia coli-induced immune paralysis is not exacerbated during chronic filarial infection. Immunology 145: 150–160.
-
144.
Duffaut C, Galitzky J, Lafontan M, Bouloumie A, 2009. Unexpected trafficking of immune cells within the adipose tissue during the onset of obesity. Biochem Biophys Res Commun 384: 482–485.
-
145.
DeFuria J et al. 2013. B cells promote inflammation in obesity and type 2 diabetes through regulation of T-cell function and an inflammatory cytokine profile. Proc Natl Acad Sci USA 110: 5133–5138.
-
146.
Hamada M, Abe M, Miyake T, Kawasaki K, Tada F, Furukawa S, Matsuura B, Hiasa Y, Onji M, 2011. B cell-activating factor controls the production of adipokines and induces insulin resistance. Obesity (Silver Spring) 19: 1915–1922.
-
147.
Tada F, Abe M, Kawasaki K, Miyake T, Shiyi C, Hiasa Y, Matsuura B, Onji M, 2013. B cell activating factor in obesity is regulated by oxidative stress in adipocytes. J Clin Biochem Nutr 52: 120–127.
-
148.
Mallat Z, 2011. The B-side story in insulin resistance. Nat Med 17: 539–540.
-
149.
Winer DA et al. 2011. B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat Med 17: 610–617.
-
150.
Chatzigeorgiou A, Karalis KP, Bornstein SR, Chavakis T, 2012. Lymphocytes in obesity-related adipose tissue inflammation. Diabetologia 55: 2583–2592.
-
151.
Finkelman FD, Katona IM, Urban JF Jr, Holmes J, Ohara J, Tung AS, Sample JV, Paul WE, 1988. IL-4 is required to generate and sustain in vivo IgE responses. J Immunol 141: 2335–2341.
-
152.
Hussaarts L, van der Vlugt LE, Yazdanbakhsh M, Smits HH, 2011. Regulatory B-cell induction by helminths: implications for allergic disease. J Allergy Clin Immunol 128: 733–739.
-
153.
Ludwig-Portugall I, Layland LE, 2012. TLRs, Treg, and B cells, an interplay of regulation during helminth infection. Front Immunol 3: 8.
-
154.
Correale J, Farez M, Razzitte G, 2008. Helminth infections associated with multiple sclerosis induce regulatory B cells. Ann Neurol 64: 187–199.
-
155.
Hussaarts L, van der Vlugt LE, Yazdanbakhsh M, Smits HH, 2011. Regulatory B-cell induction by helminths: implications for allergic disease. J Allergy Clin Immunol 128: 733–739.
-
156.
Fairfax KC, Amiel E, King IL, Freitas TC, Mohrs M, Pearce EJ, 2012. IL-10R blockade during chronic schistosomiasis mansoni results in the loss of B cells from the liver and the development of severe pulmonary disease. PLoS Pathog 8: e1002490.
-
157.
Fairfax KC, Amiel E, King IL, Freitas TC, Mohrs M, Pearce EJ, 2012. IL-10R blockade during chronic schistosomiasis mansoni results in the loss of B cells from the liver and the development of severe pulmonary disease. PLoS Pathog 8: e1002490.
-
158.
Bordon Y, 2011. Natural killer T cells: worth holding on to. Nat Rev Immunol 11: 642.
-
159.
Lynch L, Nowak M, Varghese B, Clark J, Hogan AE, Toxavidis V, Balk SP, O’Shea D, O’Farrelly C, Exley MA, 2012. Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production. Immunity 37: 574–587.
-
160.
Miyazaki Y et al. 2008. Effect of high fat diet on NKT cell function and NKT cell-mediated regulation of Th1 responses. Scand J Immunol 67: 230–237.
-
161.
Mantell BS, Stefanovic-Racic M, Yang X, Dedousis N, Sipula IJ, O’Doherty RM, 2011. Mice lacking NKT cells but with a complete complement of CD8+ T-cells are not protected against the metabolic abnormalities of diet-induced obesity. PLoS One 6: e19831.
-
162.
Lynch L, O’Shea D, Winter DC, Geoghegan J, Doherty DG, O’Farrelly C, 2009. Invariant NKT cells and CD1d(+) cells amass in human omentum and are depleted in patients with cancer and obesity. Eur J Immunol 39: 1893–1901.
-
163.
Faveeuw C, Mallevaey T, Trottein F, 2008. Role of natural killer T lymphocytes during helminthic infection. Parasite 15: 384–388.
-
164.
Mallevaey T, Zanetta JP, Faveeuw C, Fontaine J, Maes E, Platt F, Capron M, de-Moraes ML, Trottein F, 2006. Activation of invariant NKT cells by the helminth parasite Schistosoma mansoni. J Immunol 176: 2476–2485.
-
165.
Mallevaey T, Fontaine J, Breuilh L, Paget C, Castro-Keller A, Vendeville C, Capron M, Leite-de-Moraes M, Trottein F, Faveeuw C, 2007. Invariant and noninvariant natural killer T cells exert opposite regulatory functions on the immune response during murine schistosomiasis. Infect Immun 75: 2171–2180.
-
166.
Balmer P, Devaney E, 2002. NK T cells are a source of early interleukin-4 following infection with third-stage larvae of the filarial nematode Brugia pahangi. Infect Immun 70: 2215–2219.
-
167.
Galic S, Oakhill JS, Steinberg GR, 2010. Adipose tissue as an endocrine organ. Mol Cell Endocrinol 316: 129–139.
-
168.
Rasouli N, Kern PA, 2008. Adipocytokines and the metabolic complications of obesity. J Clin Endocrinol Metab 93: S64–S73.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 9 | 9 | 9 |
| Full Text Views | 894 | 211 | 2 |
| PDF Downloads | 380 | 102 | 2 |
Cell Type-Specific Immunomodulation Induced by Helminthes: Effect on Metainflammation, Insulin Resistance and Type-2 Diabetes
Recent epidemiological studies have documented an inverse relationship between the decreasing prevalence of helminth infections and the increasing prevalence of metabolic diseases (“metabolic hygiene hypothesis”). Chronic inflammation leading to insulin resistance (IR) has now been identified as a major etiological factor for a variety of metabolic diseases other than obesity and Type-2 diabetes (metainflammation). One way by which helminth infections such as filariasis can modulate IR is by inducing a chronic, nonspecific, low-grade, immune suppression mediated by modified T-helper 2 (Th2) response (induction of both Th2 and regulatory T cells) which can in turn suppress the proinflammatory responses and promote insulin sensitivity (IS). This article provides evidence on how the cross talk between the innate and adaptive arms of the immune responses can modulate IR/sensitivity. The cross talk between innate (macrophages, dendritic cells, natural killer cells, natural killer T cells, myeloid derived suppressor cells, innate lymphoid cells, basophils, eosinophils, and neutrophils) and adaptive (helper T [CD4+] cells, cytotoxic T [CD8+] cells and B cells) immune cells forms two opposing circuits, one associated with IR and the other associated with IS under the conditions of metabolic syndrome and helminth-mediated immunomodulation, respectively.
Author Notes
These authors contributed equally to this work.
Financial support: The Department of Genetics, University of Madras, has received funds for infrastructural support from DST-FIST and UGC-SAP programs. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Authors’ addresses: Vivekanandhan Aravindhan, Department of Genetics, University of Madras, Taramani Campus, Chennai, Tamil Nadu, India, E-mail: cvaravindhan@gmail.com. Gowrishankar Anand, Department of Molecular Immunology, Anna University-K B Chandrasekhar Research Centre, Chennai, Tamil Nadu, India, E-mail: anandgshankar@gmail.co.