Extracellular vesicles in host-pathogen interactions and immune regulation — exosomes as emerging actors in the immunological theater of pregnancy

Abstract

This review correlates and summarizes the role of the maternal-fetal interface in the immune tolerance of the fetus and the processes that lead to infection avoidance, emphasizing the participation of exosomes and other extracellular vesicles in both situations. Exosomes are released into the extracellular medium by several cell types and are excellent carriers of biomolecules. Host-derived exosomes and the transport of pathogen-derived molecules by exosomes impact infections in different ways. The interactions of exosomes with the maternal immune system are pivotal to a favorable gestational outcome. In this review, we highlight the potential role of exosomes in the establishment of an adequate milieu that enables embryo implantation and discuss the participation of exosomes released at the maternal-fetal interface during the establishment of an immune-privileged compartment for fetal development. The placenta is a component where important strategies are used to minimize the risk of infection. To present a contrast, we also discuss possible mechanisms used by pathogens to cross the maternal-fetal interface. We review the processes, mechanisms, and potential consequences of dysregulation in all of the abovementioned phenomena. Basic information about exosomes and their roles in viral immune evasion is also presented. The interactions between extracellular vesicles and bacteria, fungi, parasites and proteinaceous infectious agents are addressed. The discovery of the placental microbiota and the implications of this new microbiota are also discussed, and current proposals that explain fetal/placental colonization by both pathogenic and commensal microbes are addressed. The comprehension of such interactions will help us to understand the immune dynamics of human pregnancy and the mechanisms of immune evasion used by different pathogens.

Participation of Extracellular Vesicles from Zika-Virus-Infected Mosquito Cells in the Modification of Naïve Cells’ Behavior by Mediating Cell-to-Cell Transmission of Viral Elements

“…These findings suggest that both sEVs and lEVs from ZIKV-infected mosquito cells carry the viral E protein and viral RNA. Different viruses manipulate EVs for their benefit in order to increase their persistence, pathogenesis, and transmission [58][59][60][61][62]64]. The hijacking of mosquito cell membranes by ZIKV could facilitate their escape from host immune responses, promoting the viral elements' spread.…”

Beyond HIV infection: Neglected and varied impacts of CCR5 and CCR5Δ32 on viral diseases

“…The multiple roles of EVs in viral infections began to be studied more intensively in recent years, representing an emerging topic in the field of infectious diseases. Currently, the relationship between EVs and viral infections has already been explored (to a greater or lesser extent) in the context of the following viruses: Bunyaviruses, Cytomegalovirus, Dengue virus (DENV), Ebola virus, Epstein-Barr virus, Hepatitis A virus, Hepatitis C virus (HCV), Human papillomavirus, Herpes simplex virus, Human T cell lymphotropic virus, Kaposi's sarcoma-associated herpesvirus, Zika virus (ZIKV), TBEV, HIV (Kaminski et al, 2019b), and Influenza virus (Zheng et al, 2020).…”

“…EVs participate in immune evasion processes, ultimately allowing viruses to bypass host defenses (Kaminski et al, 2019b). For example, HIV is likely to usurp the exosome biogenesis pathway in such a way that enhances its infectivity, while increasing its evading strategies from the host immune defenses (Ellwanger et al, 2017a).…”

Extracellular vesicles in normal pregnancy and pregnancy‐related diseases

“…miR‐499 inhibition leads to inflammation dysregulation and increased risk of pregnancy failure in vivo . Maternal immune system is essential for the uterus to prevent pathogenic infections . Holder et al demonstrate that macrophage derived exosomes can be internalized by placental cells via clathrin‐dependent endocytosis, increasing the release of pro‐inflammatory cytokines such as IL‐6, IL‐8 and IL‐10, potentially facilitating protective placental immune responses during pregnancy.…”