Differential Association of Gene Content Polymorphisms of Killer Cell Immunoglobulin-Like Receptors with Placental Malaria in HIV- and HIV+ Mothers

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From: PLoS ONE(Vol. 7, Issue 6)
Publisher: Public Library of Science
Document Type: Article
Length: 8,376 words
Lexile Measure: 1580L

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Author(s): Yusuf O. Omosun 1 , 3 , Anna J. Blackstock 1 , 3 , Wangeci Gatei 1 , Allen Hightower 1 , Anne Maria van Eijk 4 , 6 , John Ayisi 4 , Juliana Otieno 5 , Renu B. Lal 2 , Richard Steketee 1 , Bernard Nahlen 1 , Feiko O. ter Kuile 6 , Laurence Slutsker 1 , Ya Ping Shi 1 , *


In sub-Saharan Africa, it is estimated that 32 million pregnant women are at risk for Plasmodium falciparum infection annually [1]. The placenta, in particular, is highly susceptible to the infection and malaria parasite sequesters in vascular spaces, resulting in local inflammation [2]. Parity-dependent malarial immunity is acquired over consecutive pregnancies protecting multigravid women against the adverse effect of pregnancy-associated malaria, and as a consequence, in high transmission areas susceptibility to malaria decreases with increasing gravidity, whereas in areas of low endemicity, this trend is not as evident. The public health consequences of malaria in pregnancy also vary by transmission intensity: maternal illness, preterm births and fetal loss predominate in low transmission settings whereas maternal anemia, fetal growth restriction resulting in low birth weight and subsequent increased infant mortality are commonly seen in high transmission areas [3], [4], [5]. HIV-1 infection in women of reproductive age is another major public health problem and often coexists with malaria in pregnant women in sub-Saharan Africa [6]. HIV complicates the adverse consequences of placental malaria (PM) by increasing risk of infection, parasite densities and severity of the disease [7], [8] and by impairing the response to anti-malarial therapy [9]. On the other hand, malaria infection in pregnant women increases HIV-1 viral load [10], but the effect on perinatal mother to child transmission (MTCT) of HIV is not clear. Six studies addressed whether PM enhanced MTCT and all were conducted prior to the widespread introduction of antiretrovirals (ARVs) with conflicting conclusions [11], [12], [13], [14], [15], [16], showing increased MTCT in two studies in Uganda [11], [15], no effect in two other studies at the Kenya Coast [13], [14], and a significant protective effect in Mozambique and western Kenya [12], [16].

Pregnant women have abundant Natural Killer (NK) cells in the decidua of placenta. NK cells function by cell cytolysis or by cytokine production, and their functions have been implicated in the process of placentation and as first-line innate immune defense to infection during pregnancy [17]. Previous immunological studies have shown that increased IFN-[gamma] expressing NK cells in the placenta were associated with a reduced risk of PM infection regardless of gravidity [18], and that HIV-1 infection could impair their ability to control PM, in part, by loss of IFN-[gamma] production in placenta [19]. NK cells have also been associated with protection from HIV infection [20]; however high HIV viral loads cause expansion of functional deficient NK cells [21], [22]. These results suggest that NK cell related immunity is involved in both malaria infection during pregnancy and HIV infection, and malaria co-infection with HIV could have...

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Gale Document Number: GALE|A477115203