In Utero Exposure to Filarial Antigens and Its Influence on Infection Outcomes

Abstract

The earliest potential exposure of the human host to filarial antigens is in the uterine environment. The impact of this exposure on host susceptibility and development of antifilarial immune responses following challenge with infective larvae is unclear. Although a number of studies suggest that children born to infected mothers may have a greater risk of acquiring infection than children of uninfected mothers, it has been difficult to relate these epidemiologic findings to specific alterations in antifilarial immune responsiveness. Immunologic studies of cord blood mononuclear cells (CBMC) have demonstrated that CBMC are capable of responding to crude filarial antigens with the production of a range of cytokines and parasite specific antibodies that are qualitatively similar to those produced by adults. Although these data demonstrate that sensitization to filarial antigens does take place in utero, additional work is needed to critically examine CBMC responses to defined parasite antigens and to conduct quantitative comparisons of B and T cell responses of children born to infected and uninfected mothers. In addition, it is important to consider the possibility that susceptibility to filarial infection may not depend strictly on the expression of filaria-specific immune responses per se, but may be a function of the cytokine environment in which the parasite develops. If so, in utero exposure to filarial antigens may alter this milieu.

In utero sensitization modulates IgG isotype, IFN‐γ and IL‐10 responses of neonates in bancroftian filariasis

“…The percentage of similarity of recognition pattern in the pool cord blood serum with pool of maternal blood serum was high for IgG3 response than IgG4 in all three groups. This indicates that the transfer of filarial‐specific IgG3 was more intense than IgG4 in filarial infection which is at par with the report published for normal Japanese population . Although the mothers in both the groups (M+C+ and M+C−) were infected, yet the difference in the banding pattern among them may be due to the difference in their adult worm load.…”

“…. This may directly stimulate antibody production in utero through idiotypic interactions in the absence of filarial antigens or else due to stimulation of IFN‐γ . From this finding, we hypothesize that high IFN‐γ may facilitate more transfer of filarial‐specific IgG3 in cord bloods of uninfected mothers compared with infected mothers.…”

Maternal filarial infection: association of anti-sheath antibody responses with plasma levels of IFN-γand IL-10

“…Similarly, immunological memory established by pre-natal sensitization is long-lived and the T-and B-cell responses detected in the cord blood preparations are not due to maternal lymphocytes that have passed into the fetal circulation (Malhotra et al 1999). Therefore, it is speculated that susceptibility to filarial infection may not strictly be due to the expression of filarial-specific immune responses but may be a function of the cytokine environment in which the parasite survives and develops (Lammie, 2002).…”

“…The high level of IL-10 associated with the absence of anti-sheath antibodies might be favouring the survival of the parasite during children's early exposure to infection; earlier findings have demonstrated that microfilaraemic subjects respond to parasite antigens by producing a set of suppressing cytokines (IL-10 and TGF-β) that may facilitate persistence of the parasite within humans (King et al 1993). In addition to this, in utero exposure to filarial antigen perhaps leads to subtle down-regulation of the expression of Th1-associated responses, thus promoting the establishment of patent infection (Lammie, 2002). From all those observations it is tempting to predict that high levels of IL-10 with an absence of anti-sheath antibodies in the cord bloods of infected mothers could be an evolutionary adaptation for parasite survival in their offsprings' early exposure to infection.…”

Transplacental transfer of filarial antigens fromWuchereria bancrofti-infected mothers to their offspring

“…Two cord blood samples from CFA-negative mothers were also positive for IgE antibody isotype. In the absence of filarial antigen, maternal antibody may directly stimulate antibody production in utero through idiotypic interactions (Lammie, 2002). It has been reported that chronic helminth parasite infection during pregnancy can stimulate Ag-specific B cell immunity as well as T cell memory in utero (King et al 1998).…”