Chronic schistosomiasis during pregnancy epigenetically reprograms T‐cell differentiation in offspring of infected mothers

Abstract

Schistosomiasis is a nontransplacental helminth infection. Chronic infection during pregnancy suppresses allergic airway responses in offspring.We addressed the question whether in utero exposure to chronic schistosome infection (Reg phase) in mice affects B-cell and T-cell development. Therefore, we focused our analyses on T-cell differentiation capacity induced by epigenetic changes in promoter regions of signature cytokines in offspring. Here, we show that naïve T cells from offspring of schistosome infected female mice had a strong capacity to differentiate into T H 1 cells, whereas T H 2 differentiation was impaired. In accordance, reduced levels of histone acetylation of the IL-4 promoter regions were observed in naïve T cells. To conclude, our mouse model revealed distinct epigenetic changes within the naïve T-cell compartment affecting T H 2 and T H 1 cell differentiation in offspring of mothers with chronic helminth infection. These findings could eventually help understand how helminths alter T-cell driven immune responses induced by allergens, bacterial or viral infections, as well as vaccines.Keywords: Epigenetic histone modification r In utero programming r Maternal helminth infection r Schistosomiasis r T-cell differentiation Additional supporting information may be found in the online version of this article at the publisher's web-site Over the last century and in strong contrast to developing countries, a continuous rise in allergic diseases, such as asthma, is observed in industrialized countries [1]. It is currently discussed whether helminthic parasites contribute to the low prevalence of allergic diseases in parasite endemic areas [2] due to their well-known ability to suppress bystander immune responses * These authors contributed equally to this work.

Filarial infection during pregnancy has profound consequences on immune response and disease outcome in children: A birth cohort study

“…Here we can speculate that susceptibility to filarial infection may not strictly be due to the expression of filarial specific immune responses but may be a function of the cytokine environment in which the parasite survives and develops [ 20 ]. But diminished IFN-γ response in children born to infected mother has been predicted to bias the immune response towards development of T regulatory and Th2 responses rather than Th1 responses [ 7 ].Moreover a negative correlation between IFN-γ and IL-10 observed among the infected children born to infected mother highlights epigenetic changes within the naïve T cell compartment affecting Th2 and Th1 cell differentiation as described by others in offspring of mothers with chronic helminthic infection [ 21 , 22 ]…”

Can Parasitic Worms Cure the Modern World’s Ills?

“…Of note in the context of education of (neonate) immune responses and its dysfunction in inflammatory disease, chronic S. mansoni infection during pregnancy was reflected by reduced airway hyper-responsiveness in the children. This was associated with decreased polarisation towards Th2 responses in infants that corresponded with reduced levels of histone acetylation in the IL-4 promoter regions in naive T cells [72] suggesting that maternal infection may impact on induction of immunoregulatory networks and their pathogenic dysfunction during childhood by transgenerational changes to the epigenetic landscape of immune system cells.…”

Maternal helminth infections and the shaping of offspring immunity

“…In addition, the bystander protective effects against ovalbumin‐induced airway allergy were also observed during the long‐term regulatory phase of infection with S. mansoni . Klar and colleagues observed a T helper cell intrinsic block of Th2 differentiation from naive CD4 + T cells in offspring born of these long‐term S. mansoni ‐infected mothers, which correlated with reduced histone acetylation pattern of Th2 promotor regions. As it stands, these correlative observations still lack evidence of causality and more in‐depth analyses are needed to decipher the dynamics of such epigenetic changes alongside their role in other immune response such as vaccines and bacterial or viral infections besides allergies.…”

“…It is likely that this effect is mediated by a number of mechanisms. While cytokine‐mediated exacerbation was implicated after maternal S. mansoni infection, more recent work identified epigenetic changes to offspring T cells which could play an important role in the maternal effects on offspring immunity …”

“…However, antibody transfer is not the sole mechanism by which maternal immunity is transferred to the offspring. Transfer of cytokines, antigens, changes in offspring microbiota, transfer of maternal cells or noninherited maternal antigens (NIMAs) as well as inherited or noninherited epigenetic modifications in offspring are all influenced by our mother and shape our immune system pre‐ and post‐natally. How helminth infections influence these effects represents a significantly underworked component of our understanding of the host helminth relationship.…”