Increased hepatic interleukin-1, arachidonic acid, and reactive oxygen species mediate the protective potential of peptides shared by gut cysteine peptidases against Schistosoma mansoni infection in mice.

Autor: Tallima H; Zoology Department, Faculty of Science, Cairo University, Giza, Egypt.; Department of Chemistry, School of Sciences and Engineering, The American University in Cairo, New Cairo, Cairo, Egypt., El Ridi R; Zoology Department, Faculty of Science, Cairo University, Giza, Egypt.
Jazyk: angličtina
Zdroj: PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2023 Mar 15; Vol. 17 (3), pp. e0011164. Date of Electronic Publication: 2023 Mar 15 (Print Publication: 2023).
DOI: 10.1371/journal.pntd.0011164
Abstrakt: Background: Multiple antigen peptide (MAP) construct of peptide with high homology to Schistosoma mansoni cathepsin B1, MAP-1, and to cathepsins of the L family, MAP-2, consistently induced significant (P < 0.05) reduction in challenge S. mansoni worm burden. It was, however, necessary to modify the vaccine formula to counteract the MAP impact on the parasite egg counts and vitality, and discover the mechanisms underlying the vaccine protective potential.
Methodology: Outbred mice were immunized with MAP-2 in combination with alum and/or MAP-1. Challenge infection was performed three weeks (wks) after the second injection. Blood and liver pieces were obtained on an individual mouse basis, 23 days post-infection (PI), a time of S. mansoni development and feeding in the liver before mating. Serum samples were examined for the levels of circulating antibodies and cytokines. Liver homogenates were used for assessment of liver cytokines, uric acid, arachidonic acid (ARA), and reactive oxygen species (ROS) content. Parasitological parameters were evaluated 7 wks PI.
Principal Findings: Immunization of outbred mice with MAP-2 in combination with alum and/or MAP-1 elicited highly significant (P < 0.005) reduction of around 60% in challenge S. mansoni worm burden and no increase in worm eggs' loads or vitality, compared to unimmunized or alum pre-treated control mice. Host memory responses to the immunogens are expected to be expressed in the liver stage when worm feeding and cysteine peptidases release start to be active. Serum antibody and cytokine levels were not significantly different between control and vaccinated mouse groups. Highly significant (P < 0.05 - <0.0001) increase in liver interleukin-1, ARA, and ROS content was recorded in MAP-immunized compared to control mice.
Conclusion/significance: The findings provided an explanation for the gut cysteine peptidases vaccine-mediated reduction in challenge worm burden and increase in egg counts.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 Tallima, El Ridi. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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