Monocytes from Uninfected Neonates Born to -Infected Mothers Display Upregulated Capacity to Produce TNF-α and to Control Infection in Association with Maternally Transferred Antibodies.

Activated monocytes/macrophages that produce inflammatory cytokines and nitric oxide are crucial for controlling infection. We previously showed that uninfected newborns from infected mothers (M+B- newborns) were sensitized to produce higher levels of inflammatory cytokines than newborns from uninfected mothers (M-B- newborns), suggesting that their monocytes were more activated. Thus, we wondered whether these cells might help limit congenital infection.

The macrophage infectivity potentiator of induces innate IFN-γ and TNF-α production by human neonatal and adult blood cells through TLR2/1 and TLR4.

We previously identified the recombinant (r) macrophage (M) infectivity (I) potentiator (P) of the protozoan parasite (Tc) (rTcMIP) as an immuno-stimulatory protein that induces the release of IFN-γ, CCL2 and CCL3 by human cord blood cells. These cytokines and chemokines are important to direct a type 1 adaptive immune response. rTcMIP also increased the Ab response and favored the production of the Th1-related isotype IgG2a in mouse models of neonatal vaccination, indicating that rTcMIP could be used as a vaccine adjuvant to enhance T and B cell responses.

Macrophage-infectivity potentiator of (TcMIP) is a new pro-type 1 immuno-stimulating protein for neonatal human cells and vaccines in mice.

This work identifies the protein "macrophage infectivity potentiator" of trypomastigotes, as supporting a new property, namely a pro-type 1 immunostimulatory activity on neonatal cells. In its recombinant form (rTcMIP), this protein triggers the secretion of the chemokines CCL2 and CCL3 by human umbilical cord blood cells from healthy newborns, after 24h culture. Further stimulation for 72h results in secretion of IFN-γ, provided cultures are supplemented with IL-2 and IL-18.

Epigenetic signature of exposure to maternal infection in cord blood cells from uninfected newborns.

To assess the epigenetic effects of exposure to maternal infection. We performed an epigenome-wide association study to compare the DNA methylation patterns of umbilical cord blood cells from uninfected babies from chagasic and uninfected mothers. DNA methylation was measured using Infinium EPIC arrays.