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Generation of Human Monocyte-derived Dendritic Cells from Whole Blood
Published on: December 24, 2016
Human cytomegalovirus tropism for mucosal myeloid dendritic cells
1Center for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, Oakland, CA, 94609, USA.
Abstract:
Human CMV infections are a serious source of morbidity and mortality for immunocompromised patients and for the developing fetus. Because of this, the development of new strategies to prevent CMV acquisition and transmission is a top priority. Myeloid dendritic cells (DC) residing in the oral and nasal mucosae are among the first immune cells to encounter CMV during entry and greatly contribute to virus dissemination, reactivation from latency, and horizontal spread. Albeit affected by the immunoevasive tactics of CMV, mucosal DC remain potent inducers of cellular and humoral immune responses against this virus. Their natural functions could thus be exploited to generate long-lasting protective immunity against CMV by vaccination via the oronasal mucosae. Although related, epithelial Langerhans-type DC and dermal monocyte-derived DC interact with CMV in dramatically different ways. Whereas immature monocyte-derived DC are fully permissive to infection, for instance, immature Langerhans-type DC are completely resistant. Understanding these differences is essential to design innovative vaccines and new antiviral compounds to protect these cells from CMV infection in vivo.
Insights
Developing new vaccines against human cytomegalovirus (CMV) is crucial. Targeting myeloid dendritic cells (DC) in the oronasal mucosa offers a promising strategy for preventing CMV infection and transmission.
Area of Science:
- Immunology
- Virology
- Vaccinology
Background:
- Human cytomegalovirus (CMV) infections pose significant risks to immunocompromised individuals and developing fetuses.
- Myeloid dendritic cells (DC) in mucosal tissues are critical in initial CMV encounters, dissemination, and immune response induction.
Purpose of the Study:
- To explore the potential of exploiting mucosal myeloid dendritic cells (DC) for developing novel vaccination strategies against CMV.
- To understand the differential interactions of Langerhans-type DC and monocyte-derived DC with CMV.
Main Methods:
- The study focuses on the immunological roles and interactions of myeloid dendritic cells (DC) with human cytomegalovirus (CMV).
- Comparative analysis of immature Langerhans-type DC and monocyte-derived DC susceptibility to CMV infection.
Main Results:
- Mucosal myeloid dendritic cells (DC), despite CMV's immune evasion tactics, are effective inducers of cellular and humoral immunity.
- Immature monocyte-derived DC are permissive to CMV infection, while immature Langerhans-type DC are resistant.
Conclusions:
- Harnessing the immune functions of mucosal DC via oronasal vaccination could establish long-lasting protection against CMV.
- Understanding cell-specific CMV interactions is key for designing effective vaccines and antiviral therapies.
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