Maternal Infection with Trypanosoma cruzi and Congenital Chagas Disease Induce a Trend to a Type 1 Polarization of Infant Immune Responses to Vaccines

Abstract

BackgroundWe previously showed that newborns congenitally infected with Trypanosoma cruzi (M+B+) display a strong type 1 parasite-specific T cell immune response, whereas uninfected newborns from T. cruzi-infected mothers (M+B−) are prone to produce higher levels of proinflammatory cytokines than control neonates (M−B−). The purpose of the present study was to determine if such fetal/neonatal immunological environments could alter the response to standard vaccines administered in early life.MethodologyInfants (6–7 months old) living in Bolivia, an area highly endemic for T. cruzi infection, and having received Bacillus Calmette Guerin (BCG), hepatitis B virus (HBV), diphtheria and tetanus vaccines, were enrolled into the M+B+, M+B−, M−B− groups mentioned above. The production of IFN-γ and IL-13, as markers of Th1 and Th2 responses respectively, by peripherical blood mononuclear cells stimulated with tuberculin purified protein derivative of Mycobacterium tuberculosis (PPD) or the vaccinal antigens HBs, diphtheria toxoid (DT) or tetanus toxoid (TT), as well as circulating levels of IgG antibodies against HBsAg, DT and TT were analyzed in infants. Cellular responses to the superantigen SEB were also monitored in M+B+, M+B−, M−B−infants and newborns.Principal FindingsM+B+ infants developed a stronger IFN-γ response to hepatitis B, diphtheria and tetanus vaccines than did M+B− and M−B− groups. They also displayed an enhanced antibody production to HBsAg. This was associated with a type 1-biased immune environment at birth, since cells of M+B+ newborns produced higher IFN-γ levels in response to SEB. M+B− infants produced more IFN-γ in response to PPD than the other groups. IL-13 production remained low and similar in all the three groups, whatever the subject's ages or vaccine status.ConclusionThese results show that: i) both maternal infection with T. cruzi and congenital Chagas disease do not interfere with responses to BCG, hepatitis B, diphtheria and tetanus vaccines in the neonatal period, and ii) the overcoming of immunological immaturity by T. cruzi infection in early life is not limited to the development of parasite-specific immune responses, but also tends to favour type 1 immune responses to vaccinal antigens.

Trypanosoma cruzi activates cord blood myeloid dendritic cells independently of cell infection

“…In addition, the large sub-population of parasite-uninfected mDCs activated during incubation with T. cruzi could process and present extracellular parasite antigens, as well as a large variety of T. cruzi-unrelated antigens for which immune responses would be boosted. This is supported by our previous report showing that 6-to 7-month-old infants born to T. cruzi-infected mothers display improved type 1 immune responses to BCG, HBV, diphtheria and tetanus vaccines after standard immunization [11].…”

“…One to 12% of T. cruzi-infected pregnant women transmit the parasite to their foetuses [7,8]. In previous studies, we showed that: (i) uninfected newborns from T. cruzi-infected mothers display a potent inXammatory environment [50], (ii) newborns congenitally infected with T. cruzi develop an adult-like parasite-speciWc CD8 + T cell response producing interferon(IFN)- [16] and (iii) 6-to 7-month-old infants born to T. cruzi-infected mothers displayed boosted type 1 immune responses to Bacillus Calmette Guerin (BCG), hepatitis B virus (HBV), diphtheria and tetanus vaccines after routine immunization [11]. These data point out a T. cruzi-associated immunological imprinting of immune responses in early life by maternal and/or congenital infection, overcoming immunological immaturity in early life and resulting in parasite-speciWc as well as boosted heterologous responses, such as those mounted to vaccine antigens.…”

Congenital Chagas disease as an ecological model of interactions between Trypanosoma cruzi parasites, pregnant women, placenta and fetuses

“…It includes antibodies recognizing T. cruzi (Miles et al, 1975;Breniere et al, 1983;Truyens et al, 2005;Sosa-Estani et al, 2008), as well as other microorganisms having previously infected the woman, or resulting from vaccinations (Dauby et al, 2009). The levels of T. cruzi-specific-antibodies in neonates and their repertoire are similar to those of their mothers (Breniere et al, 1983), indicating that the slight and focused placentitis often observed in chronically infected pregnant women (see Sections 6.2 and 6.3) does not affect their transfer.…”

Activation of cord blood myeloid dendritic cells by Trypanosoma cruzi and parasite-specific antibodies, proliferation of CD8+ T cells, and production of IFN-γ

“…or uninfected mothers (without T. cruzi-specific antibodies; Ab-), obtained in Bolivia from previous studies [4,33]. IgG were purified by three sequential precipitations with ammonium sulfate 33% (w/w) final concentration, washed, dialyzed against PBS, and stored in small aliquots at -20°C at a concentration of 10 mg/mL until use (to avoid IgG aggregation after repeated thawing).…”