Maternal Microchimerism Predicts Increased Infection but Decreased Disease due to Plasmodium falciparum During Early Childhood

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

<p class="first" id="d13169477e227">Placental malaria infection results in increased maternal cell and DNA trafficking to the fetus, known as maternal microchimerism, which in turn predicts increased risk of malaria infection but decreased risk of malaria disease in children. </p><div class="section"> <a class="named-anchor" id="s01">  </a> <h5 class="section-title" id="d13169477e233">Background</h5> <p id="d13169477e235">A mother’s infection with placental malaria (PM) can affect her child’s susceptibility to malaria, although the mechanism remains unclear. The fetus acquires a small amount of maternal cells and DNA known as maternal microchimerism (MMc), and we hypothesized that PM increases MMc and that MMc alters risk of <i>Plasmodium falciparum</i> malaria during infancy. </p> </div><div class="section"> <a class="named-anchor" id="s02">  </a> <h5 class="section-title" id="d13169477e241">Methods</h5> <p id="d13169477e243">In a nested cohort from Muheza, Tanzania, we evaluated the presence and level of cord blood MMc in offspring of women with and without PM. A maternal-specific polymorphism was identified for each maternal–infant pair, and MMc was assayed by quantitative polymerase chain reaction. The ability of MMc to predict malaria outcomes during early childhood was evaluated in longitudinal models. </p> </div><div class="section"> <a class="named-anchor" id="s03">  </a> <h5 class="section-title" id="d13169477e246">Results</h5> <p id="d13169477e248">Inflammatory PM increased the detection rate of MMc among offspring of primigravidae and secundigravidae, and both noninflammatory and inflammatory PM increased the level of MMc. Detectable MMc predicted increased risk of positive blood smear but, interestingly, decreased risk of symptomatic malaria and malaria hospitalization. </p> </div><div class="section"> <a class="named-anchor" id="s04">  </a> <h5 class="section-title" id="d13169477e251">Conclusions</h5> <p id="d13169477e253">The acquisition of MMc may result in increased malaria infection but protection from malaria disease. Future studies should be directed at the cellular component of MMc, with attention to its ability to directly or indirectly coordinate anti-malarial immune responses in the offspring. </p> </div>

Related collections

Most cited references 39

Record: found
Abstract: found
Article: not found

Akaike's information criterion in generalized estimating equations.

W. Pan (2001)

Correlated response data are common in biomedical studies. Regression analysis based on the generalized estimating equations (GEE) is an increasingly important method for such data. However, there seem to be few model-selection criteria available in GEE. The well-known Akaike Information Criterion (AIC) cannot be directly applied since AIC is based on maximum likelihood estimation while GEE is nonlikelihood based. We propose a modification to AIC, where the likelihood is replaced by the quasi-likelihood and a proper adjustment is made for the penalty term. Its performance is investigated through simulation studies. For illustration, the method is applied to a real data set.

0 comments Cited 408 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Maternal alloantigens promote the development of tolerogenic fetal regulatory T cells in utero.

Jeff Mold, Jakob Michaëlsson, Trevor D Burt … (2008)

As the immune system develops, T cells are selected or regulated to become tolerant of self antigens and reactive against foreign antigens. In mice, the induction of such tolerance is thought to be attributable to the deletion of self-reactive cells. Here, we show that the human fetal immune system takes advantage of an additional mechanism: the generation of regulatory T cells (Tregs) that suppress fetal immune responses. We find that substantial numbers of maternal cells cross the placenta to reside in fetal lymph nodes, inducing the development of CD4+CD25highFoxP3+ Tregs that suppress fetal antimaternal immunity and persist at least until early adulthood. These findings reveal a form of antigen-specific tolerance in humans, induced in utero and probably active in regulating immune responses after birth.

0 comments Cited 254 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Extrathymic generation of regulatory T cells in placental mammals mitigates maternal-fetal conflict.

Robert M. Samstein, Steven Z. Josefowicz, Aaron Arvey … (2012)

Regulatory T (Treg) cells, whose differentiation and function are controlled by X chromosome-encoded transcription factor Foxp3, are generated in the thymus (tTreg) and extrathymically (peripheral, pTreg), and their deficiency results in fatal autoimmunity. Here, we demonstrate that a Foxp3 enhancer, conserved noncoding sequence 1 (CNS1), essential for pTreg but dispensable for tTreg cell generation, is present only in placental mammals. CNS1 is largely composed of mammalian-wide interspersed repeats (MIR) that have undergone retrotransposition during early mammalian radiation. During pregnancy, pTreg cells specific to a model paternal alloantigen were generated in a CNS1-dependent manner and accumulated in the placenta. Furthermore, when mated with allogeneic, but not syngeneic, males, CNS1-deficient females showed increased fetal resorption accompanied by increased immune cell infiltration and defective remodeling of spiral arteries. Our results suggest that, during evolution, a CNS1-dependent mechanism of extrathymic differentiation of Treg cells emerged in placental animals to enforce maternal-fetal tolerance. Copyright © 2012 Elsevier Inc. All rights reserved.