Immunologische und entwicklungsbiolgische Auswirkungen der maternalen Helmintheninfektion auf die Nachkommen

• Antragstellerin: Professorin Dr. Clarissa Prazeres da Costa
• Fachliche Zuordnung: Pneumologie,Thoraxchirurgie ; Immunologie ; Parasitologie und Biologie der Erreger tropischer Infektionskrankheiten
• Förderung: Förderung von 2014 bis 2018
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 254868190

• Erstellungsjahr: 2019

Zusammenfassung der Projektergebnisse

Taken together we could demonstrate that offspring generated by mating of infected females during the three consecutive and distinct immune phases elicited during the course schistosomiasis (Th1, Th2 and Reg) were either partially or almost completely protected from allergic airway inflammation (AAI) or showed aggravation of the disease. Interestingly, AAI in naïve (non-offspring) BALB/c mice proved to be dependent on the Nlrp3 inflammasome, possibly opening up new avenues of treatment with IL-1beta or IL1R-antagonists. Further investigation of maternal schistosome infection revealed distinct changes in placental gene expression, cytokine environment and offspring’s early immune cell composition as well as a clear role for maternal Interferon-γ on the progeny’s protective immune phenotype. Furthermore, we were able to demonstrate that T cell development in offspring was specifically altered during in utero exposure to maternal signals elicited during the chronic (Reg) phase of infection leading to suppression of the overall capacity to develop Th2 of naïve CD4 T cells alongside epigenetic alterations at Th2 promotor regions. Newest and unpublished data reveal that the alterations are not restricted to the CD4 compartment but extend to the CD8 T cell compartment. Investigation of vaccine-induced CD8 T cell responses point towards adjuvant- and immunization route-dependent differences in CD8 responses in offspring from chronically infected female mice. The results stemming from this proposal have led to the successful grant within the funding scheme of the DFG “German-African Cooperation Project in Infectiology 2017” (Title of the project: “Assessing the effect of maternal helminth infection on Vitamin D regulation and on the immune system of the infant (HELMVIT)”) which is a collaboration with the CERMEL (Centre de la Recherche Medicale de Lambarene) in Gabon) and the Institute of Tropical Medicine, Universität Tübingen.

Projektbezogene Publikationen (Auswahl)

• Functional relevance of NLRP3 inflammasome-mediated IL-1beta during acute allergic airway inflammation. Clin Exp Immunol. 2014 Nov;178(2):212-23
  Ritter M, Straubinger K, Schmidt S, Busch D, Hagner S, Garn H, Layland L, Prazeres da Costa C
  
• Maternal Helminth Infection Determines Offspring Susceptibility to Allergic Airway Inflammation. J Allergy Clin Immunol. 2014 Dec; 134(6):1271-1279
  Straubinger K, Paul S, Prazeres da Costa O, Buch T, Busch DH, Layland L and Prazeres da Costa C
  
• Maternal helminth infections. Adv Exp Med Biol. Oct 2014;828:27-48
  Straubinger K, Prazeres da Costa C
  
• Microbes and asthma: Opportunities for intervention. J Allergy Clin Immunol. 2016 Mar;137(3):690-7
  Smits HH, Hiemstra PS, Prazeres da Costa C, Ege M, Edwards M, Garn H, Howarth PH, Jartti T, de Jong EC, Maizels RM, Marsland BJ, McSorley HJ, Müller A, Pfefferle PI, Savelkoul H, Schwarze J, Unger WW, von Mutius E, Yazdanbakhsh M, Taube C
  
• Parasites, microbiota and metabolic disease. Parasite Immunol. 2016 Oct 7
  Bhattacharjee S, Kalbfuss N, Prazeres da Costa C
  
• Chronic schistosomiasis during pregnancy epigenetically reprograms T cell differentiation in offspring of infected mothers. Eur J Immunol 2017 May;47(5):841-847
  Klar K, Perchermeier S, Bhattacharjee S, Harb H, Adler T, Istvanffy R, Loffredo-Verde E, Oostendorp R, Renz H, Prazeres da Costa C
  
• Dectin-1/2-induced autocrine PGE2 signaling licenses dendritic cells to prime Th2 responses. PLoS Biol. 2018 Apr 18;16(4):e2005504
  Kaisar MMM, Ritter M, Del Fresno C, Jónasdóttir HS, van der Ham AJ, Pelgrom LR, Schramm G, Layland LE, Sancho D, Prazeres da Costa C, Giera M, Yazdanbakhsh M, Everts B
  
• Maternal helminth infections and the shaping of offspring immunity. Parasite Immunol. 2018 Oct 29:e12599
  Dewals BG, Layland LE, Prazeres da Costa C, Horsnell WG
  
• Maternal Schistosomiasis: Immunomodulatory Effects with Lasting Impact on Allergy and Vaccine Responses; Front. Immunol.
  Lacorcia M and Prazeres da Costa C