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

Harrington, Whitney E.; Kanaan, Sami B; Muehlenbachs, Atis; Morrison, Robert; Stevenson, Philip A.; Fried, Michal; Duffy, Patrick E.; Nelson, J. Lee

doi:10.1093/infdis/jix129

Cited by 30 publications

(28 citation statements)

References 49 publications

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“…A notable finding of this paper is that maternal micro-chimerism was more profound in these preterm babies, thus providing additional evidence of inflammation-driven increase in maternal micro-chimerism. The same authors reported earlier that fetuses with severe congenital diaphragmatic hernia, who exhibit high inflammatory cytokines in cord blood, also have increased maternal micro-chimerism (7); a similar increase was also described in babies exposed to placental malaria (8). Interestingly, the latter study showed that both malaria infection and inflammation contributed to this enhanced transfer of maternal cells.…”

supporting

confidence: 64%

Human fetal immune cells fight back

Chougnet

2018

Sci. Transl. Med.

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supporting

confidence: 64%

Human fetal immune cells fight back

Chougnet

2018

Sci. Transl. Med.

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“…This may permit larger molecules or even cells to enter into the fetal circulation. 42,48 Once across the syncytiotrophoblast barrier, it is unclear how exogenous antigens traverse the fetal endothelium, which represents the last barrier to entry into the fetal bloodstream, although FcgRI on endothelial cells could play a role. Presumably, malaria antigens and/ or immune complexes are subsequently taken up by fetal APCs, although this process has received little or no research attention.…”

Section: Mal Aria Anti G En E Xp Osure I N Uteromentioning

confidence: 99%

“…54 PM has been associated with higher levels of maternal microchimerism in cord blood, particularly when placental histopathology shows evidence of significant inflammation. 48 The short-and long-term consequences of this maternal microchimerism for infant immunity have not yet been fully explored, but increased induction of T regs during gestation could lead to dampened pathogen-specific immunity. It has also been noted that cord blood immune cell populations, including T-cells, B-cells, NK cells, and monocytes frequently include cells of maternal origin, which are particularly enriched among memory T-cells.…”

Section: Pl Acental Mal Aria and Maternal Microchimeris Mmentioning

confidence: 99%

The immune response to malaria in utero

Feeney

2019

Immunological Reviews

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Malaria caused by Plasmodium falciparum is a leading killer of infants and children. Efforts to develop a protective vaccine have been hindered by the parasite's numerous evasion strategies, which include the induction of immunoregulatory mechanisms in the human host.Indeed, several promising vaccine candidates that induce robust protection in malaria-naive populations have been shown to have much lower efficacy when administered to individuals residing in endemic settings, 1,2 suggesting that immunomodulatory mechanisms induced by prior malaria exposure may pose a critical barrier to vaccine-mediated protection. In endemic regions, many individuals are first exposed to malaria in utero, when P. falciparum-infected red blood cells sequester in the placenta and parasite antigens cross the syncytiotrophoblast barrier, gaining entry into the fetal circulation.Therefore, even during the neonatal period, vaccination may be influenced by prior malaria exposure. Here, we examine the consequences of in utero antigen exposure for fetal immune development and postnatal immunity. The worldwide burden posed by malaria-related complications of pregnancy is profound. More than 125 million pregnancies occur annually in regions at risk for malaria transmission, 3 and one in four pregnant women in sub-Saharan Africa have evidence of infection with malaria at parturition. 4 Although most placental malaria (PM) infections are attributable to P. falciparum, recent evidence indicates that P.vivax is also associated with poor pregnancy outcomes, and some data suggest that it too may sequester in the placenta. 5,6 Pregnancy-associated malaria results in tremendous obstetrical and pediatric morbidity, AbstractMalaria causes tremendous early childhood morbidity and mortality, providing an urgent impetus for the development of a vaccine that is effective in neonates. However, the infant immune response to malaria may be influenced by events that occur well before birth. Placental malaria infection complicates one quarter of all pregnancies in Africa and frequently results in exposure of the fetus to malaria antigens in utero, while the immune system is still developing. Some data suggest that in utero exposure to malaria may induce immunologic tolerance that interferes with the development of protective immunity during childhood. More recently, however, a growing body of evidence suggests that fetal malaria exposure can prime highly functional malariaspecific T-and B-cells, which may contribute to postnatal protection from malaria. In utero exposure to malaria also impacts the activation and maturation of fetal antigen presenting cells and innate lymphocytes, which could have implications for global immunity in the infant. Here, we review recent advances in our understanding of how various components of the fetal immune system are altered by in utero exposure to malaria, discuss factors that may tilt the critical balance between tolerance and adaptive immunity, and consider the implications of these findings for malaria prevention strateg...

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“…Based on the hypothesis that malaria infection results in inflammation and pathologic changes as well as alterations in VEGF expression in the placenta, the association between PM and maternal microchimerism was recently examined . The investigators found that inflammatory PM was associated with an increased prevalence of maternal microchimerism and that both inflammatory and noninflammatory PM were associated with increased level of maternal microchimerism.…”

Section: Maternal Malaria Shapes the Maternal To Foetal Graftmentioning

confidence: 99%

Malaria in pregnancy shapes the development of foetal and infant immunity

Harrington

Kakuru

Jagannathan

2018

Parasite Immunology

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Malaria, particularly Plasmodium falciparum, continues to disproportionately affect pregnant women. In addition to the profoundly deleterious impact of maternal malaria on the health of the mother and foetus, malaria infection in pregnancy has been shown to affect the development of the foetal and infant immune system and may alter the risk of malaria and nonmalarial outcomes during infancy. This review summarizes our current understanding of how malaria infection in pregnancy shapes the protective components of the maternal immune system transferred to the foetus and how foetal exposure to parasite antigens impacts the development of foetal and infant immunity. It also reviews existing evidence linking malaria infection in pregnancy to malaria and nonmalarial outcomes in infancy and how preventing malaria in pregnancy may alter these outcomes. A better understanding of the consequences of malaria infection in pregnancy on the development of foetal and infant immunity will inform control strategies, including intermittent preventive treatment in pregnancy and vaccine development.

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

Abstract: 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.

Cited by 30 publications

References 49 publications

Human fetal immune cells fight back

Human fetal immune cells fight back

The immune response to malaria in utero

Malaria in pregnancy shapes the development of foetal and infant immunity

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