A Proinflammatory Immune Response Might Determine Toxoplasma gondii Vertical Transmission and Severity of Clinical Features in Congenitally Infected Newborns.

Toxoplasma gondii is the etiological agent of toxoplasmosis. Mother-to-child transmission of this parasite can occur during pregnancy. Newborns with congenital toxoplasmosis may develop central nervous system impairment, with severity ranging from subclinical manifestations to death. A proinflammatory/regulated specific immune profile is crucial in the defense against the parasite; nevertheless, its role in the infected pregnant women and the congenitally infected offspring has been poorly explored, and there is still no consensus about its relation to parasite vertical transmission or to severity and dissemination in the congenitally infected newborns. This work aimed to characterize these relations by means of principal component and principal factor analyses. For this purpose, we determined the specific production of the four immunoglobulin G antibody subclasses, cytokines, and lymphocyte proliferation in the T. gondii-infected pregnant women-10 who transmitted the infection to their offspring and seven who did not-as well as in 11 newborns congenitally infected and grouped according to disease severity (five mild and six moderate/severe) and dissemination (four local and seven disseminated). We found that the immune response of nontransmitter women differed from that of the transmitters, the latter having a stronger proinflammatory response, supporting a previous report. We also found that newborns who developed moderate/severe disease presented higher levels of lymphocyte proliferation, particularly of CD8+ and CD19+ cells, a high proportion of tumor necrosis factor α producers, and reduced expression of the immune modulator transforming growth factor ß, as opposed to children who developed mild clinical complications. Our results suggest that a distinctive, not regulated, proinflammatory immune response might favor T. gondii vertical transmission and the development of severe clinical manifestations in congenitally infected newborns.

Maternal Immune Response During Pregnancy and Vertical Transmission in Human Toxoplasmosis.

Toxoplasmosis is a parasitic zoonosis distributed worldwide, caused by the ingestion of contaminated water/food with the parasite Toxoplasma gondii. If a pregnant woman is infected with this parasite, it may be transmitted to the fetus and produce ocular, neurological, or systemic damage with variable severity. The strength and profile of mother's immune response have been suggested as important factors involved in vertical transmission rate and severity of clinical outcome in the congenitally infected fetus. The aim of this work was to evaluate a possible relation between the mother's immune response during pregnancy and congenital transmission to the fetus. We obtained peripheral blood from T. gondii infected pregnant woman and tested it for anti T. gondii (IgG1, IgG2, IgG3, IgG4, and IgA) in serum. Peripheral blood mononuclear cells (PBMCs) were isolated to analyze the in vitro effect of soluble T. gondii antigens on proliferation and production of cytokines. We found that IgG2-4 and IgA antibodies and lymphocytes proliferation, especially CD4+, CD8+, and CD19+ were positive in a higher proportion of cases in transmitter than in non-transmitter women. Furthermore, IgG2-3 and IgA anti-Toxoplasma antibody levels were higher in those mothers who transmitted the infection than in those who did not. Interestingly, a higher proportion of positive cases to IFN-γ and negatives to the immunoregulatory cytokine TGF-ß, were related to T. gondii vertical transmission. Our descriptive results are consistent with the paradoxical previous observations in murine models of congenital toxoplasmosis, which suggest that an increased immune response that protects the mothers from a disseminated or severe disease, and should protect the fetus from infection, is positively related to parasite transmission.