Journal List > J Bacteriol Virol > v.46(4) > 1034236

J Bacteriol Virol. 2016 Dec;46(4):295-302. Korean.
Published online December 31, 2016.  https://doi.org/10.4167/jbv.2016.46.4.295
Copyright © 2016 The Korean Society for Microbiology and The Korean Society of Virology
Eosinophils Regulate Type 2 Immune Responses Following Infection with the Nematode Trichinella spiralis
Jayoung Koo and YunJae Jung
Department of Microbiology, School of Medicine, Gachon University, Incheon, Korea.

Corresponding author: YunJae Jung, MD, PhD. Department of Microbiology, School of Medicine, Gachon University, 155 Gaetbeol-ro, Yeonsu-gu, Incheon 21999, Korea. Phone: +82-32-899-6415, Fax: +82-32-899-6039, Email: yjjung@gachon.ac.kr
Received December 02, 2016; Revised December 03, 2016; Accepted December 06, 2016.

This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/).


Abstract

Eosinophils are multifunctional leukocytes implicated in protection against helminth infections. Although eosinophils comprise between 1~5% of peripheral blood leukocytes, they primarily reside in the gastrointestinal tract under homeostatic conditions, and rapidly proliferate upon parasitic infection. Intestinal infection with Trichinella spiralis (T. spiralis) induces eosinophilia when the parasite enters the larval stages and larvae finally migrate to the skeletal muscle. Eosinophils are known to mediate parasite death through antibody-dependent cellular cytotoxicity. In this study, we aimed to address the functional significance of eosinophils in the intestinal phase of T. spiralis infection by analysis of immune responses in the Peyer's patch (PP) of infected BALB/c and eosinophil-ablated ΔdblGATA mice. Trafficking of eosinophils to the PP was significantly increased, with upregulation of interleukin-5 at 14 days post infection. Eosinophil deficiency led to a significant augmentation of serum immunoglobulin (Ig) M and IgG1 antibody levels. In accordance with this, IgG1+ B cells in the PP were substantially increased in ΔdblGATA mice compared to that in BALB/c mice. Transforming growth factor-β expression in the PP of infected ΔdblGATA mice was significantly decreased compared to that in BALB/c mice, whereas the number of T. spiralis larvae in the diaphragm was increased. Taken together, these findings indicate that eosinophils contribute to the regulation of Th2 immune responses, and protect the host from T. spiralis attempting to establish larvae in the skeletal muscle.

Keywords: Eosinophils; Trichinella spiralis; Intestinal phase; Peyer's patch; Th2 responses

Figures


Figure 1
Increased eosinophil frequency in the spleen and Peyer's patch (PP) by Trichinella spiralis (T. spiralis) infection. (A and B) Frequency of CCR3+SiglecF+ eosinophils in the spleen (A) and PP (B) of BALB/c and ΔdblGATA mice at 14 days post infection (dpi). Data represent mean ± s.e.m. values. A two-group comparison was performed by a Student's t-test. *p < 0.05, **p < 0.01, ***p < 0.001.
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Figure 2
Increased total and Trichinella-specific immunoglobulin (Ig) levels after T. spiralis infection. (A and B) Total (A) and Trichinella-specific (B) IgM, IgG1, and IgG2a titers in sera of BALB/c and ΔdblGATA mice at 14 dpi. Data represent mean ± s.e.m. values. A two-group comparison was performed by a Student's t-test. *p < 0.05, **p < 0.01.
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Figure 3
Increased isotype responses in the PP after T. spiralis infection. (A and B) Frequency of CD3+, B220+, IgG1+, and IgG2a+ cells in the spleen (A) and PP (B) of BALB/c and ΔdblGATA mice at 14 dpi. The frequency of IgG1+ and IgG2a+ cells was analyzed with B220-gated cells. (C) Frequency of PNAhigh cells in the PP of BALB/c and ΔdblGATA mice at 14 dpi. Data are mean ± s.e.m. values. A two-group comparison was performed by a Student's t-test. *p < 0.05, **p < 0.01, ***p < 0.001.
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Figure 4
Immune responses in the PP and muscle larvae after T. spiralis infection. (A) mRNA expression of cytokine in the PP of BALB/c and ΔdblGATA mice at 14 dpi. (B) Hematoxylin and eosin stained sections of diaphragm collected from BALB/c and ΔdblGATA mice at 14 dpi. Arrows indicate representative T. spiralis larvae in the diaphragm. Numbers of larvae per five fields were counted with three sections of each group of mice. Original magnification ×40. Data are mean ± s.e.m. values. A two-group comparison was performed by a Student's t-test. *p < 0.05, **p < 0.01.
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Notes

This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2016R1D1A1A09916492). The author thanks Dr. So-Youn Woo (Ewha Womans University, Korea) for supporting works with ΔdblGATA mice. T. spiralis was kindly provided by Dr. Hee-Jae Cha (Kosin University, Korea). The author thanks to Eun-Hui Lee (Gachon University, Korea) for technical assistance.

References
1. Jung Y. Eosinophils are required for immune responses induced by oral immunization. J Bacteriol Virol 2015;45:354–363.
2. Rothenberg ME, Hogan SP. The eosinophil. Annu Rev Immunol 2006;24:147–174.
3. Yu C, Cantor AB, Yang H, Browne C, Wells RA, Fujiwara Y, et al. Targeted deletion of a high-affinity GATA-binding site in the GATA-1 promoter leads to selective loss of the eosinophil lineage in vivo. J Exp Med 2002;195:1387–1395.
4. Jung Y, Rothenberg ME. Roles and regulation of gastrointestinal eosinophils in immunity and disease. J Immunol 2014;193:999–1005.
5. Rosenberg HF, Phipps S, Foster PS. Eosinophil trafficking in allergy and asthma. J Allergy Clin Immunol 2007;119:1303–1310.
6. Lee TD. Helminthotoxic responses of intestinal eosinophils to Trichinella spiralis newborn larvae. Infect Immun 1991;59:4405–4411.
7. Kazura JW, Aikawa M. Host defense mechanisms against Trichinella spiralis infection in the mouse: eosinophil-mediated destruction of newborn larvae in vitro. J Immunol 1980;124:355–361.
8. Specht S, Saeftel M, Arndt M, Endl E, Dubben B, Lee NA, et al. Lack of eosinophil peroxidase or major basic protein impairs defense against murine filarial infection. Infect Immun 2006;74:5236–5243.
9. Kita H. The eosinophil: a cytokine-producing cell? J Allergy Clin Immunol 1996;97:889–892.
10. Jacobsen EA, Helmers RA, Lee JJ, Lee NA. The expanding role(s) of eosinophils in health and disease. Blood 2012;120:3882–3890.
11. Goh YP, Henderson NC, Heredia JE, Red Eagle A, Odegaard JI, Lehwald N, et al. Eosinophils secrete IL-4 to facilitate liver regeneration. Proc Natl Acad Sci U S A 2013;110:9914–9919.
12. Heredia JE, Mukundan L, Chen FM, Mueller AA, Deo RC, Locksley RM, et al. Type 2 innate signals stimulate fibro/adipogenic progenitors to facilitate muscle regeneration. Cell 2013;153:376–388.
13. Wu D, Molofsky AB, Liang HE, Ricardo-Gonzalez RR, Jouihan HA, Bando JK, et al. Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science 2011;332:243–247.
14. Shin MH. Eosinophil and tissue-invasive parasitic helminth. Hanyang Med Rev 2010;30:238–245.
15. Harley JP, Gallicchio V. Trichinella spiralis: migration of larvae in the rat. Exp Parasitol 1971;30:11–21.
16. Despommier D. Adaptive changes in muscle fibers infected with Trichinella spiralis. Am J Pathol 1975;78:477–496.
17. Bruschi F, Korenaga M, Watanabe N. Eosinophils and Trichinella infection: toxic for the parasite and the host? Trends Parasitol 2008;24:462–467.
18. Venturiello SM, Giambartolomei GH, Costantino SN. Immune cytotoxic activity of human eosinophils against Trichinella spiralis newborn larvae. Parasite Immunol 1995;17:555–559.
19. Kazura JW, Grove DI. Stage-specific antibody-dependent eosinophil-mediated destruction of Trichinella spiralis. Nature 1978;274:588–589.
20. Gebreselassie NG, Moorhead AR, Fabre V, Gagliardo LF, Lee NA, Lee JJ, et al. Eosinophils preserve parasitic nematode larvae by regulating local immunity. J Immunol 2012;188:417–425.
21. Fabre V, Beiting DP, Bliss SK, Gebreselassie NG, Gagliardo LF, Lee NA, et al. Eosinophil deficiency compromises parasite survival in chronic nematode infection. J Immunol 2009;182:1577–1583.
22. Huang L, Appleton JA. Eosinophils in Helminth Infection: Defenders and Dupes. Trends Parasitol 2016;32:798–807.
23. Grove DI, Mahmoud AA, Warren KS. Eosinophils and resistance to Trichinella spiralis. J Exp Med 1977;145:755.
24. Mowat AM. Anatomical basis of tolerance and immunity to intestinal antigens. Nat Rev Immunol 2003;3:331–341.
25. Mishra A, Hogan SP, Brandt EB, Rothenberg ME. Peyer's patch eosinophils: identification, characterization, and regulation by mucosal allergen exposure, interleukin-5, and eotaxin. Blood 2000;96:1538–1544.
26. Franssen FF, Fonville M, Takumi K, Vallée I, Grasset A, Koedam MA, et al. Antibody response against Trichinella spiralis in experimentally infected rats is dose dependent. Vet Res 2011;42:113.
27. Coico RF, Bhogal BS, Thorbecke GJ. Relationship of germinal centers in lymphoid tissue to immunologic memory. VI. Transfer of B cell memory with lymph node cells fractionated according to their receptors for peanut agglutinin. J Immunol 1983;131:2254–2257.
28. Masterson JC, McNamee EN, Fillon SA, Hosford L, Harris R, Fernando SD, et al. Eosinophil-mediated signalling attenuates inflammatory responses in experimental colitis. Gut 2015;64:1236–1247.
29. Chen Z, Andreev D, Oeser K, Krljanac B, Hueber A, Kleyer A, et al. Th2 and eosinophil responses suppress inflammatory arthritis. Nat Commun 2016;7:11596.
30. Beiting DP, Gagliardo LF, Hesse M, Bliss SK, Meskill D, Appleton JA. Coordinated control of immunity to muscle stage Trichinella spiralis by IL-10, regulatory T cells, and TGF-beta. J Immunol 2007;178:1039–1047.