Chapter 15 - Hofbauer cells and placental viral infection

Abstract

The human placenta acts as a physical barrier between the maternal and fetal circulatory systems, and is key in the protection against vertical transmission of viral infection. Hofbauer cells are fetal placental macrophages that are located in the mesenchyme adjacent to the fetal capillaries. Hofbauer cells support angiogenesis and villous development. In the setting of placental infection, the Hofbauer cells play a role in protection against vertical transmission of microbes. They sequester virions to contain and irradicate pathogen-induced pathologic variants. Focusing on two viruses in pregnancy, Zika virus (ZIKV), a single-stranded RNA virus, and human immunodeficiency virus (HIV), a double-stranded RNA retrovirus, sequestration of the virus occurs in the Hofbauer cells. However, productive infections may occur and increase the vertical transmission risk. With ZIKV infection of Hofbauer cells, pattern recognition receptors (PRPs) recognize viral RNA and trigger an innate immune response initially targeted at controlling viral replication. However, as it is known, ZIKV vertical transmission can occur and lead to a congenital Zika syndrome in the fetus and newborn that includes microcephaly, craniofacial and ocular abnormalities, and seizures. Similar to ZIKV infection in pregnancy, HIV virus is also identified to be sequestered in Hofbauer cells within the placenta. Following the natural history of disease, without antiretroviral therapy, vertical transmission would only occur in 7%. The Hofbauer cells express both CD4 and HIV coreceptors DC-SIGN, CCR5, and CXCR4. The CD4 receptor binds the viral glycoprotein(gp), gp120. The gp41 protein then fuses with the cell membrane to facilitate entry into the Hofbauer cell. Following entry of the Hofbauer cell, its cytokine response plays a critical role in preventing or permitting vertical transmission. We conclude that placental Hofbauer cells play a key role in ZIKV and HIV infection during pregnancy.