Fetomaternal immune crosstalk modifies T cell priming through sustained changes to DC function.

Lacorcia, Matthew; Bhattacharjee, Sonakshi; Laubhahn, Kristina; Alhamdan, Fahd; Ram, Marija; Muschaweckh, Andreas; Potaczek, Daniel P; Kosinska, Anna; Garn, Holger; Protzer, Ulrike; Renz, Harold; Prazeres da Costa, Clarissa

BACKGROUND Prenatal exposure to infections can modify immune development. These environmental disturbances during early life potentially alter the incidence of inflammatory disorders as well as priming of immune responses. Infection with the helminth Schistosoma mansoni is widely studied for its ability to alter immune responsiveness, and associated with variations in co-infection, allergy, and vaccine efficacy in endemic populations. OBJECTIVE Exposure to maternal schistosomiasis during early life, even without transmission of infection, can result in priming effects on offspring immune responses to bystander antigenic challenges as relate to allergic responsiveness and vaccination, with this work seeking to clarify further effects and underlying immunological imprinting. METHODS Here, we combine a chronic maternal schistosomiasis infection model with a thorough analysis of subsequent offspring immune responses to allergy and vaccination models, including viral challenge and steady state changes to immune cell compartments. RESULTS We demonstrate that maternal schistosomiasis alters CD4+ responses during allergic sensitization and challenge, in a skewed IL-4/B-cell-dominant response to antigenic challenge associated with limited inflammatory response. Beyond that, we uncover previously unidentified alterations to CD8+ T cell responses during immunization, dependent upon vaccine formulation, that have functional impact upon the efficacy of vaccination against viral infection in a murine Hepatitis B virus model. CONCLUSION Alongside steady-state modifications to CD4+ T cell polarization and B cell priming, we trace these modified CD8+ responses to an altered dendritic cell phenotype sustained into adulthood, providing evidence for complex priming effects imparted by infection via fetomaternal crosstalk.