Gestation and breastfeeding in schistosomotic mothers differently modulate the immune response of adult offspring to postnatal Schistosoma mansoni infection

Abstract

Schistosoma mansoni antigens in the early life alter homologous and heterologous immunity during postnatal infections. We evaluate the immunity to parasite antigens and ovalbumin (OA) in adult mice born/suckled by schistosomotic mothers. Newborns were divided into: born (BIM), suckled (SIM) or born/suckled (BSIM) in schistosomotic mothers, and animals from noninfected mothers (control). When adults, the mice were infected and compared the hepatic granuloma size and cellularity. Some animals were OA + adjuvant immunised. We evaluated hypersensitivity reactions (HR), antibodies levels (IgG1/IgG2a) anti-soluble egg antigen and anti-soluble worm antigen preparation, and anti-OA, cytokine production, and CD4+FoxP3+T-cells by splenocytes. Compared to control group, BIM mice showed a greater quantity of granulomas and collagen deposition, whereas SIM and BSIM presented smaller granulomas. BSIM group exhibited the lowest levels of anti-parasite antibodies. For anti-OA immunity, immediate HR was suppressed in all groups, with greater intensity in SIM mice accompanied of the remarkable level of basal CD4+FoxP3+T-cells. BIM and SIM groups produced less interleukin (IL)-4 and interferon (IFN)-g. In BSIM, there was higher production of IL-10 and IFN-g, but lower levels of IL-4 and CD4+FoxP3+T-cells. Thus, pregnancy in schistosomotic mothers intensified hepatic fibrosis, whereas breastfeeding diminished granulomas in descendants. Separately, pregnancy and breastfeeding could suppress heterologous immunity; however, when combined, the responses could be partially restored in infected descendants.

Regulação de Doenças Autoimunes mediadas pelo Schistosoma mansoni / Regulation of Autoimmune Diseases mediated by Schistosoma mansoni

“…Quando o parasita evolui para a fase adulta tem-se a oviposição, em que os antígenos solúveis dos ovos (semelhantes à self) são liberados na corrente sanguínea, provocando a inversão de uma resposta Th1 para Th2, a partir da produção de IL-4, IL-5 e IL-10, o que promove a liberação de IgE, IgG1 e IgG4. Vale ressaltar que essa resposta está associada à ativação das células Treg e da IL-10, responsáveis por controlar a reação granulomatosa ao redor dos ovos do parasita (SANTOS et al, 2016;GUIMARÃES et al, 2019).…”

Maternal Schistosomiasis: Immunomodulatory Effects With Lasting Impact on Allergy and Vaccine Responses

“…Multiple sources show indications that maternal schistosomiasis in murine systems reduces adaptive immune responses to antigens, but these are highly dependent upon the specific modes and time points of exposure to maternal infection during pregnancy. There are however conflicting reports of an altogether opposite effect (increased humoral response) contributed by breastmilk (72, 73) of schistosome infected murine mothers, although the effects of this may be dependent on the specific models used and timepoints employed. In fact, mating infected female mice during early patent infection (as opposed to the late chronic phase), where there is a strong increase in type 2 cytokines, yields increased allergic responsiveness in offspring (71).…”

Maternal helminth infections and the shaping of offspring immunity

“…However, using cross‐fostering experiments, breastfeeding from S. mansoni ‐infected mothers provided a better control of chronic hepatic disease. Whether such observation involves transfer of antigens and/or other mediators has not been defined . In addition to the impact on helminth immunity in offspring, maternal exposure to helminth infection also alters the immune response against heterologous antigens.…”