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Antibody and cytokine response to Cystoisospora suis infections in immune-competent young pigs

BACKGROUND: To date, investigations on the immune response to Cystoisospora suis infections focused on suckling piglets, the age group clinically most affected. Actively immunizing piglets is unfeasible due to their immature immune system and the typically early infection in the first days after bir...

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Autores principales: Freudenschuss, Barbara, Ruttkowski, Bärbel, Shrestha, Aruna, Abd-Elfattah, Ahmed, Pagès, Marc, Ladinig, Andrea, Joachim, Anja
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031197/
https://www.ncbi.nlm.nih.gov/pubmed/29973271
http://dx.doi.org/10.1186/s13071-018-2974-6
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author Freudenschuss, Barbara
Ruttkowski, Bärbel
Shrestha, Aruna
Abd-Elfattah, Ahmed
Pagès, Marc
Ladinig, Andrea
Joachim, Anja
author_facet Freudenschuss, Barbara
Ruttkowski, Bärbel
Shrestha, Aruna
Abd-Elfattah, Ahmed
Pagès, Marc
Ladinig, Andrea
Joachim, Anja
author_sort Freudenschuss, Barbara
collection PubMed
description BACKGROUND: To date, investigations on the immune response to Cystoisospora suis infections focused on suckling piglets, the age group clinically most affected. Actively immunizing piglets is unfeasible due to their immature immune system and the typically early infection in the first days after birth. Therefore, understanding and possibly enhancing the immune response of immune-competent animals is the prerequisite to develop a passive immunization strategy for piglets which currently rely on very limited treatment options. METHODS: To investigate antibody and cytokine responses of immune-competent animals and the impact of the oral immunization protocol on their immune response, growers with unknown previous exposure to C. suis (10–11 weeks-old) were infected one or three times with different doses (600 and 6000 or 200 and 2000, respectively) of C. suis oocysts, and compared to uninfected controls. Oocyst excretion was evaluated, and blood and intestinal mucus antibody titers were determined by IFAT. Systemic production of Th1, Th2, inflammatory and regulatory cytokines was determined in different immune compartments at mRNA and (after stimulation with a recombinant merozoite-protein) at protein level by PCR and multiplex fluorescent immunoassay, respectively. RESULTS: Infection generated significantly increased serum IgA and IgG levels against C. suis sporozoites and merozoites, irrespective of infection mode, with IgG against merozoites showing the strongest increase. No clinical signs and only occasional excretion were observed. The systemic cytokine response to C. suis was only weak. Nonetheless, in white blood cells, IL-4, IL-6 and IL-10 mRNA-levels significantly increased after infection, whereas IFN-ɣ, IL-2 and TGF-β expression tended to decrease. In mesenteric lymph nodes (MLN), IL-10 and TNF-α levels were elevated while splenic cytokine expression was unaltered upon infection. Stimulated MLN-derived lymphocytes from infected pigs produced slightly more IL-12 and less IFN-α than controls. CONCLUSIONS: An infection and a subsequent systemic immune response can be induced in immune-competent animals by all evaluated infection models and growers can be used as models to mimic sow immunizations. The immune response to C. suis, although mild and with considerable variation in cytokine expression, was characterized by a Th2-associated and regulatory cytokine profile and antibody production. However, none of the parameters clearly stood out as a potential marker associated with protection. Antibody titers were significantly positively related with oocyst excretion and might thus serve as correlates for parasite replication or severity of infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13071-018-2974-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-60311972018-07-11 Antibody and cytokine response to Cystoisospora suis infections in immune-competent young pigs Freudenschuss, Barbara Ruttkowski, Bärbel Shrestha, Aruna Abd-Elfattah, Ahmed Pagès, Marc Ladinig, Andrea Joachim, Anja Parasit Vectors Research BACKGROUND: To date, investigations on the immune response to Cystoisospora suis infections focused on suckling piglets, the age group clinically most affected. Actively immunizing piglets is unfeasible due to their immature immune system and the typically early infection in the first days after birth. Therefore, understanding and possibly enhancing the immune response of immune-competent animals is the prerequisite to develop a passive immunization strategy for piglets which currently rely on very limited treatment options. METHODS: To investigate antibody and cytokine responses of immune-competent animals and the impact of the oral immunization protocol on their immune response, growers with unknown previous exposure to C. suis (10–11 weeks-old) were infected one or three times with different doses (600 and 6000 or 200 and 2000, respectively) of C. suis oocysts, and compared to uninfected controls. Oocyst excretion was evaluated, and blood and intestinal mucus antibody titers were determined by IFAT. Systemic production of Th1, Th2, inflammatory and regulatory cytokines was determined in different immune compartments at mRNA and (after stimulation with a recombinant merozoite-protein) at protein level by PCR and multiplex fluorescent immunoassay, respectively. RESULTS: Infection generated significantly increased serum IgA and IgG levels against C. suis sporozoites and merozoites, irrespective of infection mode, with IgG against merozoites showing the strongest increase. No clinical signs and only occasional excretion were observed. The systemic cytokine response to C. suis was only weak. Nonetheless, in white blood cells, IL-4, IL-6 and IL-10 mRNA-levels significantly increased after infection, whereas IFN-ɣ, IL-2 and TGF-β expression tended to decrease. In mesenteric lymph nodes (MLN), IL-10 and TNF-α levels were elevated while splenic cytokine expression was unaltered upon infection. Stimulated MLN-derived lymphocytes from infected pigs produced slightly more IL-12 and less IFN-α than controls. CONCLUSIONS: An infection and a subsequent systemic immune response can be induced in immune-competent animals by all evaluated infection models and growers can be used as models to mimic sow immunizations. The immune response to C. suis, although mild and with considerable variation in cytokine expression, was characterized by a Th2-associated and regulatory cytokine profile and antibody production. However, none of the parameters clearly stood out as a potential marker associated with protection. Antibody titers were significantly positively related with oocyst excretion and might thus serve as correlates for parasite replication or severity of infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13071-018-2974-6) contains supplementary material, which is available to authorized users. BioMed Central 2018-07-04 /pmc/articles/PMC6031197/ /pubmed/29973271 http://dx.doi.org/10.1186/s13071-018-2974-6 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Freudenschuss, Barbara
Ruttkowski, Bärbel
Shrestha, Aruna
Abd-Elfattah, Ahmed
Pagès, Marc
Ladinig, Andrea
Joachim, Anja
Antibody and cytokine response to Cystoisospora suis infections in immune-competent young pigs
title Antibody and cytokine response to Cystoisospora suis infections in immune-competent young pigs
title_full Antibody and cytokine response to Cystoisospora suis infections in immune-competent young pigs
title_fullStr Antibody and cytokine response to Cystoisospora suis infections in immune-competent young pigs
title_full_unstemmed Antibody and cytokine response to Cystoisospora suis infections in immune-competent young pigs
title_short Antibody and cytokine response to Cystoisospora suis infections in immune-competent young pigs
title_sort antibody and cytokine response to cystoisospora suis infections in immune-competent young pigs
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031197/
https://www.ncbi.nlm.nih.gov/pubmed/29973271
http://dx.doi.org/10.1186/s13071-018-2974-6
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