Immunobiology of Acute Chorioamnionitis

Abstract

Acute chorioamnionitis is characterized by neutrophilic infiltration and inflammation at the maternal fetal interface. It is a relatively common complication of pregnancy and can have devastating consequences including preterm labor, maternal infections, fetal infection/inflammation, fetal lung, brain, and gastrointestinal tract injury. In this review, we will discuss current understanding of the pathogenesis, immunobiology, and mechanisms of this condition. Most commonly, acute chorioamnionitis is a result of ascending infection with relatively low-virulence organisms such as the Ureaplasma species. Furthermore, recent vaginal microbiome studies suggest that there is a link between vaginal dysbiosis, vaginal inflammation, and ascending infection. Although less common, microorganisms invading the maternal-fetal interface via hematogenous route (e.g., Zika virus, Cytomegalovirus, and Listeria) can cause placental villitis and severe fetal inflammation and injury. We will provide an overview of the knowledge gleaned from different animal models of acute chorioamnionitis and the role of different immune cells in different maternal-fetal compartments. Lastly, we will discuss how infectious agents can break the maternal tolerance of fetal allograft during pregnancy and highlight the novel future therapeutic approaches.

Keywords: animal model; fetal membrane; immune cells; infection; inflammation.

Figure 1

H&E histology of intrauterine inflammations. (A,B) Cross sections of human fetal membranes H&E histology showing neutrophil infiltration. Chorioamnionitis is characterized by infiltration of (D) CD68+ macrophages and (F) neutrophils expressing Myeloperoxidase+ (MPO) predominantly located at the choriodecidua junction. Note relatively much fewer CD68 or MPO expressing cells in the no chorioamnionitis group (C,E). Insets in (B,D,F) show higher power magnification of demarcated area in white and demonstrate inflammatory cells including neutrophils and macrophages.

Figure 2

Chorioamnionitis during second trimester. Higher documentation of histologic vs. clinically diagnosed chorioamnionitis in the same mothers whose Infants were born at 22–28 weeks Gestational Age (GA) in the NICHD funded Neonatal Network database (2003-2007). Also note that chorioamnionitis is more frequently diagnosed at earlier gestations (inverse correlation of gestational age with incidence of chorioamnionitis). Adapted from Stoll et al. (23).

Figure 3

Model for pathogenesis of intrauterine infection/inflammation. Representative cells in the different tissue layers of fetal membrane are shown. The left panel in figure depicts normal pregnancy and the right panel shows changes during IUI. Inflammatory products and microbial products (red dots) in the amniotic fluid and choriodecidua activate the amnion and chorion, resulting in the release of neutrophil chemoattractant (CXCL-8/IL-8 and CSF3) in a IL-1 and TNF-dependent manner. Neutrophils accumulate at choriodecidua junction, get activated, and greatly amplify the inflammation at the maternal-fetal interface with cross-talk with other immune and resident cells.