Congenital and acquired toxoplasmosis: diversity and role of antibodies in different compartments of the host

Abstract

The apicomplexan parasite Toxoplasma gondii is remarkable in several aspects, since it is a protozoan that infects most nucleated cells in many warm-blooded animals, worldwide. Although the cellular immune response against T. gondii is critical for infection control, antibodies may either enhance or block protective mechanisms, and even mediate immunological damage, directly or indirectly. Since cytokines regulate the class/subclass switch, antibodies may also be the biomarkers of protective or pathological cellular immune events. There is a scientific and clinical interest in the presence of natural and autoreactive antibodies, as well as in the 'chronic' immunoglobulin M (IgM) response and the post-treatment 'rebound'. Another interesting aspect is compartmentalization; certain immunoglobulins may uniquely be found in specific host fluids. Local synthesis has been demonstrated, but antibodies may also traverse several cell layers, like the blood-brain and haemato-ocular barriers, and the placenta. In some instances, Fc receptors (FcRs) facilitate transport and may even have a concentrator effect, which can be related to resistance or pathology. These aspects of the humoral response against T. gondii are reviewed in the present paper.

Congenital toxoplasmosis: candidate host immune genes relevant for vertical transmission and pathogenesis

“…19,20 Antibodies and their Fc receptors (FcRs) have important roles as well. 21,22 Antibodies of the immunoglobulin (Ig)A, IgM and IgG1 (equivalent to murine IgG2a) classes protect through neutralization, complement activation, opsonization of phagocytes or NK-ADCC. IgG2 and IgG4 are poor complement fixative subclasses and of low affinity for FcRs, and thus they are not expected to relate to protection.…”

“…Similarly, IgE antibodies are related to lymphadenopathy in the acute phase. 22 Once the parasite encysts, the Th1/Th17 responsedriven inflammatory reactions are downregulated, avoiding inflammatory damage. This is mediated by IL-10, transforming growth factor-b (TGF-b) and IL-27.…”

“…88 Evidence from the rodent toxoplasmosis models and functional correspondence of humans Igs and FcRs to those of mice suggest that fetal alleles associated with high serum levels of Igs, or with strong Ig/FcR binding would be related to better clinical outcome in the fetus, although they could also be related to an exacerbated, that is, damaging response. 22 Some polymorphisms of the human Fc receptors and their hypothetical effects are listed in Table 2. Eight genes transcribed in different mRNAs have been recognized.…”

“…Only IgE is commonly related to bad clinical prognosis, and IgG4 could have either negative or no influence. 7,22,100,101 The few studies on the role of anti-T. gondii antibodies on congenital infections indicate that fetuses or newborns who produce specific IgG2, IgG4 or IgE have bad clinical prognosis. 7,22,100,101…”

“…2 The changes in endocrine phenomena occurring during pregnancy, as well as the size and maturity of the placenta and of the embryonic/fetal immune response certainly affect the ability to be protected from invasion or to fight infection. [3][4][5] The size of the inoculum is also relevant for congenital infection risk and disease severity. Besides, the genetic background of the mother and the product is likely to influence outcome.…”