30th Annual Meeting of the German Society for Parasitology

Prof. Dr.

MSc.

Univ.-Prof. Dr. rer. nat.

Age-dependent rise in IFN-γ competence undermines effective type 2 responses to intestinal nematode infection

Abstract text Protective type-2 immunity against helminth infection is impaired in experimental systems biased for the production of the type-1 cytokine IFN-γ. Upon birth, Th1-like memory phenotype (MP) cells generated in the absence of infection rapidly expand and accumulate over time. We hence asked whether a rise of IFN-γ competence along host age affects the development of protective type-2 responses in mice infected with the small intestinal nematode H. polygyrus. Th1 cells expanded significantly in lymphoid and mucosal tissue with host age in uninfected BALB/c mice. Consequently, BALB/c mice infected at the age of 3-9 months displayed more extensive induction of IFN-γ competent, nematode-specific Th2/1 hybrid cells compared to younger animals. In more susceptible C57BL/6 mice, Th1 cells accumulated more rapidly at steady state, translating to elevated Th2/1 differentiation and poor control of parasite fitness in primary infections experienced at a young age. Blocking of IFN-γ and IL-12 signals during the first week of nematode infection leads to sharply decreased Th2/1 differentiation and promoted resistance in both mouse lines, whereas young BALB/c mice treated with IFN-γ at the onset of infection mirrored the Th2/1 hybrid-biased responses of older BALB/c as well as young C57BL/6 mice. Together, these data show that the spontaneous accumulation of IFN-γ competent, type 1 like effector cells progressively curtails the effectiveness of anti-nematode type 2 responses with rising host age. However, elevated IFN-γ signaling early during nematode infection strongly promotes the differentiation and systemic accumulation of GATA-3+T-bet+ Th2/1 hybrid cells rather than restraining the GATA-3+ effector T cell response. In part, more extensive systemic responses in IFN-γ-rich environments could be explained by impaired colonization of effector cells in the gut alongside the restricted expansion of Foxp3+ T cells.

Parasite Immunology

Parasite-Host Interaction

Talk

Prof.Dr.

Prevalence of Ascaris suum and hepatitis E virus co-infections in fattening pigs in Germany

Abstract text A.Laubschat1, N. Langkabel2, D. Meemken2, S. Hartmann1, J. Schlosser-Brandenburg1 1Department of Veterinary Medicine, Institute of Immunology, Centre for Infection Medicine, Freie Universität Berlin, Berlin, Germany 2Department of Veterinary Medicine, Institute of Food Safety and Food Hygiene, Section Meat Hygiene, Freie Universität Berlin, Berlin, Germany Introduction: Ascaris suum is one of the most important and prevalent helminths in pigs and causes high economic losses due to weight loss in fattening pigs and liver discard at the slaughterhouse. Hepatitis E virus (HEV) is an RNA virus of the Hepeviridae family and is of considerable public health interest since domestic pigs and wild boars are the major reservoir hosts for the zoonotic genotypes HEV-3 and HEV-4. The Therefore, consumption of raw or inadequately cooked pork/liver or contact with virus-containing feces may pose a risk for human infection. Despite the frequent occurrence of both zoonotic agents in pigs, there are no studies on the prevalence of coinfection in pig herds and its impact on virus replication and shedding. Pigs have few- to no clinical symptoms which is why infections in farms remain undetected. Although both pathogens are prevalent in domestic pigs and considerable interested of public health there is no investigation yet about the effects of a Co-infection of both pathogens. Objectives: Our hypothesis is that pig herds in which A. suum is prevalent have an increased HEV prevalence and are therefore at higher risk for zoonotic transmission. Here we assume that Th2 immunity induced by migratory worm larvae counteracts the antiviral Th1-mediated immune response in the liver. Material and Methods: To determine the prevalence of coinfections in German pig herds, slaughterhouse samples from fattening pigs (n=500) are serologically examined by ELISA and screened for viral RNA by qRT-PCR. Acute worm infestation of the liver is pathognomically diagnosed on the basis of milk spots. Conclusion: This study will provide a first insight into the prevalence of coinfection in German fattening pigs. Based on our data, new approaches could be developed to reduce HEV transmission through targeted Ascaris control strategies. This is highly relevant for the food safety of pork/liver, as well as for the exposure of veterinarians, slaughterhouse personnel and farmers.

Veterinary Parasitology

Dynamics of mucosal and systemic Th2 / Th1 effector T cells in response to tissue migrating Ascaris suum infections

Abstract text Introduction: The large roundworm Ascaris suum is one of the most relevant and frequent soil-transmitted helminths observed in pigs. Commonly, early infection and constant reinfection with A. suum can be observed. However, initial infection factors that may influence the development of efficient type 2 immune responses during larval migration are poorly understood. Here, we investigated the local and systemic adaptive immunity along the hepatotracheal migration route of Ascaris suum during primary infection in growing pigs. Materials &amp; methods: German-Landrace crossbreds were inoculated orally with a single dose of 4000 A. suum ova and dissected at different time points post before patent infection was established. Immunophenotyping for type 2 and 1 signatures was performed on PBMC and spleen and compared to local responses in nematode-migration affected tissues (liver, lung, small intestine, and their corresponding lymph nodes). In addition, Ascaris-specific CD4+ Th cells and their cytokine profile were assessed. Results: Our initial data indicate that systemic Th2 levels remain constantly low during larval migration. Contrarily, we found local and transient Th2 responses in the lungs and lungLN, but not in the liver of infected animals after A. suum L3 had migrated through these tissues. The initial invasion of the small intestine did not elicit a type 2 response. However, Th2 cells accumulated locally with the return of larvae and their maturation into pre-adult worms. Interestingly, robust Th1 responses developed both in the circulation and in most of the investigated organs and draining lymph nodes. However, at all stages of infection, the majority of CD4+ T cells directly recognizing A. suum antigens produced high levels of IL-4. Meanwhile, parasite-specific IFN-g+ T cells were less frequently observed. Conclusion: Our findings show that in growing pigs primary, experimental infection with A. suum does not induce a fulminant systemic type 2 response, but locally and kinetically restricted Th2 immunity. Because Th2 cells are known to orchestrate an efficient anti-parasite response, we propose that the ubiquitous and potentially infection-driven type 1 immune signature observed in conventionally raised pigs holds back the development of a strong type 2 response. Thus, further research is currently ongoing to evaluate if the weak type 2 immunity observed might contribute to susceptibility and constant reinfection observed in domestic pigs.

Vector-borne parasites Dirofilaria repens and Babesia canis: haematological indices and immune response profiles in naturally infected and co-infected dogs

Abstract text Co-infections with Dirofilaria repens and Babesia canis are rarely reported in the literature and there is very limited knowledge of their impact on canine health. Central Poland is endemic for both parasites, posing a risk of co-infections in dogs. Our aim was to determine the effect of co-infection on canine health. We also tested the hypothesis that infection with filariae would drive the host response towards Th2-type immunity. This in turn should result in a reduction of proinflammatory Th1-type responses that are crucial for the elimination of intracellular pathogens, such as B. canis. To evaluate the impact of co-infection on canine health, four groups of dogs were examined: healthy dogs, dogs infected with B. canis, dogs infected with D. repens and co-infected dogs. Blood parameters indicative of anaemia, kidney and liver damage were analysed statistically. Expression levels of immune response genes were determined and compared by qPCR reaction, in order to determine the type of immune response in mono-infection and co-infection. In dogs infected with D. repens, no major alterations in blood parameters were observed. Dogs infected with B. canis suffered from anaemia, kidney and liver insufficiency. Co-infected dogs showed milder alternation in blood biochemical parameters associated with liver (ALP activity) and kidney (serum urea and creatinine levels) dysfunction, compared to dogs infected only with B. canis. The expression of genes associated with cellular (Th1-mediated) (STAT4 and INF-γ), humoral (Th2-mediated) (STAT6, GATA3, SOCS3, IL-13) and regulatory IL-10 responses was quantified. All the tested factors, except INF-γ, were found to be expressed in dogs infected with D. repens. The expression of IL-13 was predominant in dogs infected with D. repens, and the expression of STAT6 and IL-10 predominated in dogs with co-infections. In summary, with just a few exceptions, no major alterations were found in blood parameters in D. repens infected dogs, and these dogs predominantly expressed Th2-related factors. While some features of Th1, T-regulatory and Th2 responses were observed in co-infected dogs, the Th2-related response appeared to predominate in these animals, and values of biochemical parameters were closer to those of healthy dogs than those solely infected with B. canis, suggesting a milder course of babesiosis in these animals. The study was funded by the National Science Centre (NCN) OPUS grant no. 2017/27/B/NZ6/01691

Session XIII
Parasite Immunology III – Helminths 2

Appointment

Chairs

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Session XIIIParasite Immunology III – Helminths 2

Appointment

Chairs

Programme

Session XIII
Parasite Immunology III – Helminths 2