J Bacteriol Virol.  2016 Dec;46(4):295-302. 10.4167/jbv.2016.46.4.295.

Eosinophils Regulate Type 2 Immune Responses Following Infection with the Nematode Trichinella spiralis

• Koo J
• Jung Y

• KMID: 2366876
• DOI: http://doi.org/10.4167/jbv.2016.46.4.295

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.

Keyword

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

MeSH Terms

Animals
B-Lymphocytes
Diaphragm
Eosinophilia
Eosinophils*
Gastrointestinal Tract
Helminths
Immunoglobulin G
Immunoglobulins
Interleukin-5
Larva
Leukocytes
Mice
Muscle, Skeletal
Parasites
Trichinella spiralis*
Trichinella*
Up-Regulation
Immunoglobulin G
Immunoglobulins
Interleukin-5

Figure

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  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.

• 

  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.

• 

  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.

• 

  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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