Abstract
BackgroundTo 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.MethodsTo 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.ResultsInfection 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.ConclusionsAn 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.
Highlights
To date, investigations on the immune response to Cystoisospora suis infections focused on suckling piglets, the age group clinically most affected
Overall, our findings indicate that the infection of immune-competent animals with C. suis does induce a systemic immune response, irrespective of infection dose or frequency, without clinical signs and with negligible oocyst excretion
The induction of an immune response without clinical signs or oocyst excretion is an ideal situation for a passive vaccination strategy
Summary
Investigations on the immune response to Cystoisospora suis infections focused on suckling piglets, the age group clinically most affected. 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. Isospora suis) occurs worldwide at high prevalences, with neonates and suckling piglets being susceptible to clinical disease [1,2,3,4]. Oocysts as resistant environmental stages, together with a high morbidity rate, make neonatal porcine cystoisosporosis one of the major causes of diarrhea in piglet production, resulting in impaired weight gain and subsequently reduced, uneven weaning weights [5, 6], and inflicting serious financial losses to the farming industry [7,8,9]. The necessity of new strategies to combat this parasitic disease, possibly targeting the immune system, has dramatically increased
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