Maternal schistosomiasis alters costimulatory molecules expression in antigen-presenting cells from adult offspring mice

Abstract

Adult offspring of Schistosoma mansoni-infected mice showed alterations in immunity to a heterologous antigen, ovalbumin (OA). Prior breastfeeding induced increased production of anti-OA antibodies, while pregnancy impaired it. Here, we investigated the expression of costimulatory molecules on antigen-presenting cells (APCs) of the adult offspring of S. mansoni-infected mothers in response to OA. Newborn mice were divided into three groups: animals Born Infected Mothers (BIM) suckled by non-infected mothers; animals from non-infected mothers Suckled Infected Mothers (SIM); and another group of mice born from and suckled by non-infected mothers (CONTROL). The adult offspring were immunized with subcutaneous OA+adjuvant, and 3-8days following immunization, double labeling was performed (CD45R/B220 or CD11c and CD80, CD86, CD40 or HLA-DR) on spleen cells. In comparison to the CONTROL group, an early increased frequency of CD40+/CD80+ B cells was observed in SIM mice (p<0.001/p<0.05), but no alteration of CD11c+ cells was observed. In contrast, in BIM mice, the frequency of CD86+/CD11c+ cells (p<0.05) and CD40+/CD80+/CD86+ B cells (p<0.01/p<0.01/p<0.05) was drastically reduced. In conclusion, previous suckling by S. mansoni-infected mothers enabled improved antigen presentation by B cells in adult offspring, whereas gestation in these mothers imprinted offspring with weak antigen presentation by APCs during the immune response to a non-related antigen.

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

“…Whether parasite antigens in the breast milk in contact with the suppressive intestinal mucosa microenvironment ( Weiner et al 2011) may collaborate for enhanced CD4 + FoxP3 + T-cells generation after antigenic re-exposure as adults deserve further investigations. Intriguingly, in SIM mice, we observed higher CD40 + CD80 + B-cells frequency and greater IL-2 production after OA stimulation ( Santos et al 2010, 20 , 2014 ), which are conditions to favour increased frequency of CD4 + FoxP3 + T-cells ( Zheng et al 2010) . Besides of this, the contact with anti-SEA antibodies at a young age can generate idiotypes and antiidiotypes that negatively modulate granulomatous reactions ( Caldas et al 2008) , and only passive transfer by breastfeeding, but not pregnancy, maintains the levels of anti-SEA IgG1 in the early in life ( Nóbrega et al 2012) .…”

“…Postnatal infection of animals pre-exposed to parasite antigens in utero strongly impairs both anti-OA Th1/IFN-g and Th2/IL-4 responses. Recently, we reported reduced expression of the co-stimulatory molecule CD86 in response to OA by CD11c + cells of adult animals born from infected mothers ( Santos et al 2014) that may have reduced capacity to prime anti-OA Th1 and Th2 responses.…”

Gestation and breastfeeding in schistosomotic mice differentially alters the expression of histone deacetylases (HDACs) in adult offspring

“…Maternal infection by S. mansoni can alter the degree of immune competence of the offspring in the long term, either through in-utero contact or breastfeeding. (2,3,4,5) In this study, the effects of gestation and breastfeeding were evaluated separately in S. mansoni-infected mothers. Therefore, the expression of HDACs, and cytokine production by lymphocytes and macrophages was assessed.…”

“…It is known that the immunological status of schistosomotic mothers can induce long-term alterations in the immune response of the offspring. (2,3,4,5) An experimental study on the effects of gestation and breastfeeding in infected mothers, separately, showed that gestation in these mothers led to potential immunosuppression in adult offspring, with elevated production of IL-10 and lower levels of anti-ovalbumin (OA) antibodies. (2) In addition, offspring born to infected mothers had a lower frequency of B lymphocytes, and the capacity for antigen presentation by CD11c+ cells was partially impaired.…”

“…(2) In addition, offspring born to infected mothers had a lower frequency of B lymphocytes, and the capacity for antigen presentation by CD11c+ cells was partially impaired. (3) In contrast, it has also been observed that adult mice pre-viously breastfed by schistosomotic mothers exhibited improvement in the production of anti-OA antibodies (2) and in the antigen presentation ability of B lymphocytes through an increase in surface frequency of CD40+/ CD80+ in these cells. (3) However, whether these alterations in the immune response of adult offspring from infected mothers are due to epigenetic changes from the perinatal period remains unclear.…”