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Shinjiro Hamano
Nagasaki University Graduate School of Biomedical Sciences
Corresponding Author
ORCiD: https://orcid.org/0000-0003-3881-8337
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Schistosomes are trematode worms that dwell in their definitive host’s blood vessels, where females lay eggs that need to be eliminated in the environment with host excreta to maintain their life cycle. Both worms and eggs require type 2 immunity for their maturation and excretion, respectively. However, immune molecules that orchestrate such immunity remain unclear. IL-33 is one of the epithelium-derived cytokines that induce type 2 immunity in tissues. This study aimed at determining its role in the maturation, reproduction, and excretion of S. mansoni eggs, and in the maintenance of egg-induced pathology in the intestines of mice.
Methods: Using S. mansoni-infected IL-33-deficient (IL-33-/-) and wild-type (WT) mice, worm morphology, reproduction, and egg excretion were studied at different time points of infection. IL-5 and IL-13 production in spleens and mesenteric lymph nodes were measured. Tissue histology was performed on the terminal ilea of non- and infected mice.
Results: Morphology-wise, worms from IL-33-/- and WT mice at the fourth and sixth weeks of infection did not differ. The worms' reproduction, expressed as eggs per worm pair, as well as the excretion of eggs, expressed as the number of eggs in intestinal tissues, did not differ between IL-33-/- and WT mice. In the sixth week of infection, IL-33-/- mice presented impaired type 2 immunity in intestines, characterized by decreased production of IL-5 and IL-13 in mesenteric lymph nodes and fewer inflammatory infiltrates with fewer eosinophils in the ilea. Besides, there was no difference between IL-33-/- and WT mice in the levels of IL-25 and TSLP in intestinal tissues.
Conclusions: Despite its ability to initiate type 2 immunity in tissues, IL-33 alone seems dispensable for S. mansoni maturation, reproduction, and egg excretion. The transient impairment of type 2 immunity observed in the intestines, but not spleens, highlights the importance of IL-33 over IL-25 and TSLP in initiating, but not maintaining, locally induced type 2 immunity in intestinal tissues in schistosome infection. Further studies are needed to decipher the role of each of them in schistosomiasis and clarify the possible interactions that might exist between them.
Keywords
IL-33, Schistosoma mansoni, worm maturation and reproduction, egg excretion, type 2 immunity, egg-induced pathology
Figure 1
Figure 2
Figure 3
Figure 4
This is a list of supplementary files associated with this preprint. Click to download.
- Fig.S1..png
Fig. S1. IL-33 deficiency does not affect the liver egg burden in S. mansoni infection. Female IL-33-/- and WT BALB/c mice (4-8 animals per group) were subcutaneously infected with 50 and 35 S. mansoni cercariae, respectively for nine and 12 weeks and sacrificed at six, nine and 12 weeks of infection to assess the number of liver tissue eggs. The number of eggs per gram of liver tissue was determined. Experiments were replicated at least three times. Data are representative of 2 independent experiments with similar results and are presented as mean with SEM. Groups were compared using unpaired two-tail t-test with Welch’s correction at p<0.05 significance. wpi=week post-infection. Related to fig. 1. Additional file 1 (PNG 18.9 KB).
- Fig.S2..png
Fig. S2. Oviposition in S. mansoni infection induces intestinal production of IL-25 and TSLP but not IL-33. Female WT BALB/c mice (3 animals per group) were subcutaneously infected with 50 and 35 S. mansoni cercariae, respectively for nine and 12 weeks and sacrificed on week 0 (Naïve), from week one to week four, then every two weeks until week 12 of infection. Small intestines were homogenized with gentleMACS Octo Dissociator and the cytokines were measured in the homogenate supernatants by ELISA. Related to fig. 4. Additional file 2 (PNG 37.1 KB).
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CURRENT STATUS: Published
View the published article at Parasites & Vectors.
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Editorial decision: Accept
On 20 Dec, 2020
Reviewers invited
Invitations sent on 07 Dec, 2020
Reviewer #1 agreed
On 07 Dec, 2020
Review #1 received
Received 07 Dec, 2020
Editor assigned
On 06 Dec, 2020
Submission checks complete
On 06 Dec, 2020
Editor invited
On 06 Dec, 2020
Version 1
Posted 17 Aug, 2020
No comments provided
Editorial decision: Major Revision
On 06 Nov, 2020
Review #3 received
Received 23 Oct, 2020
Review #2 received
Received 23 Oct, 2020
Reviewer #3 agreed
On 01 Oct, 2020
Reviewer #2 agreed
On 30 Sep, 2020
Review #1 received
Received 07 Sep, 2020
Reviewers invited
Invitations sent on 25 Aug, 2020
Reviewer #1 agreed
On 25 Aug, 2020
Editor invited
On 13 Aug, 2020
Editor assigned
On 13 Aug, 2020
First submitted
On 12 Aug, 2020
Submission checks complete
On 12 Aug, 2020
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Subject Areas
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A new preprint design is coming!
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See the published version of this preprint at Parasites & Vectors.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Shinjiro Hamano
Nagasaki University Graduate School of Biomedical Sciences
Corresponding Author
ORCiD: https://orcid.org/0000-0003-3881-8337
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Parasites & Vectors.
No community comments so far
Editorial decision: Accept
On 20 Dec, 2020
Reviewers invited
Invitations sent on 07 Dec, 2020
Reviewer #1 agreed
On 07 Dec, 2020
Review #1 received
Received 07 Dec, 2020
Editor assigned
On 06 Dec, 2020
Submission checks complete
On 06 Dec, 2020
Editor invited
On 06 Dec, 2020
Version 1
Posted 17 Aug, 2020
No comments provided
Editorial decision: Major Revision
On 06 Nov, 2020
Review #3 received
Received 23 Oct, 2020
Review #2 received
Received 23 Oct, 2020
Reviewer #3 agreed
On 01 Oct, 2020
Reviewer #2 agreed
On 30 Sep, 2020
Review #1 received
Received 07 Sep, 2020
Reviewers invited
Invitations sent on 25 Aug, 2020
Reviewer #1 agreed
On 25 Aug, 2020
Editor invited
On 13 Aug, 2020
Editor assigned
On 13 Aug, 2020
First submitted
On 12 Aug, 2020
Submission checks complete
On 12 Aug, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Parasitology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Parasites & Vectors.
Background: Schistosomes are trematode worms that dwell in their definitive host’s blood vessels, where females lay eggs that need to be eliminated in the environment with host excreta to maintain their life cycle. Both worms and eggs require type 2 immunity for their maturation and excretion, respectively. However, immune molecules that orchestrate such immunity remain unclear. IL-33 is one of the epithelium-derived cytokines that induce type 2 immunity in tissues. This study aimed at determining its role in the maturation, reproduction, and excretion of S. mansoni eggs, and in the maintenance of egg-induced pathology in the intestines of mice.
Methods: Using S. mansoni-infected IL-33-deficient (IL-33-/-) and wild-type (WT) mice, worm morphology, reproduction, and egg excretion were studied at different time points of infection. IL-5 and IL-13 production in spleens and mesenteric lymph nodes were measured. Tissue histology was performed on the terminal ilea of non- and infected mice.
Results: Morphology-wise, worms from IL-33-/- and WT mice at the fourth and sixth weeks of infection did not differ. The worms' reproduction, expressed as eggs per worm pair, as well as the excretion of eggs, expressed as the number of eggs in intestinal tissues, did not differ between IL-33-/- and WT mice. In the sixth week of infection, IL-33-/- mice presented impaired type 2 immunity in intestines, characterized by decreased production of IL-5 and IL-13 in mesenteric lymph nodes and fewer inflammatory infiltrates with fewer eosinophils in the ilea. Besides, there was no difference between IL-33-/- and WT mice in the levels of IL-25 and TSLP in intestinal tissues.
Conclusions: Despite its ability to initiate type 2 immunity in tissues, IL-33 alone seems dispensable for S. mansoni maturation, reproduction, and egg excretion. The transient impairment of type 2 immunity observed in the intestines, but not spleens, highlights the importance of IL-33 over IL-25 and TSLP in initiating, but not maintaining, locally induced type 2 immunity in intestinal tissues in schistosome infection. Further studies are needed to decipher the role of each of them in schistosomiasis and clarify the possible interactions that might exist between them.
Figure 1
Figure 2
Figure 3
Figure 4
This is a list of supplementary files associated with this preprint. Click to download.
- Fig.S1..png
Fig. S1. IL-33 deficiency does not affect the liver egg burden in S. mansoni infection. Female IL-33-/- and WT BALB/c mice (4-8 animals per group) were subcutaneously infected with 50 and 35 S. mansoni cercariae, respectively for nine and 12 weeks and sacrificed at six, nine and 12 weeks of infection to assess the number of liver tissue eggs. The number of eggs per gram of liver tissue was determined. Experiments were replicated at least three times. Data are representative of 2 independent experiments with similar results and are presented as mean with SEM. Groups were compared using unpaired two-tail t-test with Welch’s correction at p<0.05 significance. wpi=week post-infection. Related to fig. 1. Additional file 1 (PNG 18.9 KB).
- Fig.S2..png
Fig. S2. Oviposition in S. mansoni infection induces intestinal production of IL-25 and TSLP but not IL-33. Female WT BALB/c mice (3 animals per group) were subcutaneously infected with 50 and 35 S. mansoni cercariae, respectively for nine and 12 weeks and sacrificed on week 0 (Naïve), from week one to week four, then every two weeks until week 12 of infection. Small intestines were homogenized with gentleMACS Octo Dissociator and the cytokines were measured in the homogenate supernatants by ELISA. Related to fig. 4. Additional file 2 (PNG 37.1 KB).
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