Are Pregnant Women with Chronic Helminth Infections More Susceptible to Congenital Infections?

SOME SIMILARITIES BETWEEN IMMUNE RESPONSE DURING PREGNANCY AND CHRONIC HELMINTH INFECTIONS EXIST Pregnancy is a unique immunological status with different hormonal and immunological alterations. Pregnancy hormones (including progesterone, glucocorticoids, estradiol, and estriol) increase over the course of pregnancy and significantly modulate the immunological shift that occurs over the three trimesters of pregnancy (1). In contrast, helminth infections are the most common infectious diseases in developing countries. Soiltransmitted helminths (ascariasis, trichuriasis, and hookworm), schistosomiasis, and lymphatic filariasis are the most common helminthiasis. Most helminth infections have minor clinical symptoms; thus, the infection is left untreated and may remain chronic for multiple years (2). It is well-documented that a woman’s immune response during pregnancy and chronic helminth infections shift toward Type 2 immunity and anti-inflammatory cytokines (1, 3–6). During pregnancy, the activities of CD4+ T cells into helper T cell type 2 (Th2) and their anti-inflammatory cytokines [including interleukin-4 (IL-4), IL-5, and IL-10] increase. Inversely, the activities of T-helper 1 (Th1) cells and their inflammatory cytokines [as well as inflammatory macrophages and natural killer (NK) cells] decrease (1). These immunological shifts away from inflammatory responses are necessary for a successful pregnancy (1, 3). For example, activating cytotoxic cells (including NK or T cells and inflammatory cytokines such as IFN-γ and TNF-α) can damage the placenta and fetus (3). Moreover, the elevation of anti-inflammatory factors like IL-10 can prevent spontaneous abortions in murine models (7). Similar to immune response during pregnancy, the immune response during a helminth infection shifts toward Th2 and anti-inflammatory status. During chronic helminth infections, the increased activation and expansion of CD4+ Th2 cells (including eosinophils, mast cells, basophils, and the antibody isotypes IgG1, IgG4, and IgE) occur. Moreover, production of the cytokines IL-4, IL-5, IL-9, IL-10, IL-13, and IL-21 and transforming growth factor-β (TGF-β) increases (4, 5). On the other hand, several studies in murine models reveal that helminth infections manipulate host hormones for its own benefit [reviewed in Ref. (8)]. In the case of Taenia crassiceps infection (a model for human cysticercosis), infected female mice showed an increase estrogen levels after 8 weeks post-infection. Infected male also showed increase serum estradiol and decrease testosterone levels. These hormonal changes lead to increase parasite density in both genders (9). Progesterone treatment in mice with T. crassiceps infection increased parasite loads and expression of the Th2 cytokine profile (IL-4, IL-6, and IL-10) in both genders (10). These findings reveal that female sex hormones are favorable for T. crassiceps infection and the infection is associated with Type 2 immunity. Hormonal regulation during helminth infections is often associated with increased parasite survival and Type 2 immunity [reviewed in Ref. (11, 12)], which negatively affect immune response to intracellular pathogens. In contrast to immune response during pregnancy and chronic helminth infections, the protective immune response against the majority of the intracellular pathogens are mediated by Th1 cells and their cytokines (including IFN-γ, TNFα, and IL-1) (13). Furthermore, increased activation and expansion of cytotoxic CD8+ T cells, NK cells, neutrophils, and macrophages occur during infection with intracellular pathogens (4, 13). Therefore, immune system during pregnancy or helminth infections gives a weaker response to the infections that require strong Th1 immune response. So, it is plausible that a pregnant woman with chronic helminth infections is more susceptible to acquiring congenital infections due to synergic immunoregulatory effects of pregnancy and chronic helminth infections (see the next sections).