Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
, 11 (9)

Dendritic Cells (DCs) as "Fire Accelerants" of Hantaviral Pathogenesis

Affiliations
Review

Dendritic Cells (DCs) as "Fire Accelerants" of Hantaviral Pathogenesis

Günther Schönrich et al. Viruses.

Abstract

Hantaviruses are widespread zoonotic pathogens found around the globe. Depending on their geographical location, hantaviruses can cause two human syndromes, haemorrhagic fever with renal syndrome (HFRS) or hantavirus pulmonary syndrome (HPS). HPS and HFRS have many commonalities amongst which excessive activation of immune cells is a prominent feature. Hantaviruses replicate in endothelial cells (ECs), the major battlefield of hantavirus-induced pathogenesis, without causing cytopathic effects. This indicates that a misdirected response of human immune cells to hantaviruses is causing damage. As dendritic cells (DCs) orchestrate antiviral immune responses, they are in the focus of research analysing hantavirus-induced immunopathogenesis. In this review, we discuss the interplay between hantaviruses and DCs and the immunological consequences thereof.

Keywords: antiviral immune responses; dendritic cells; hantaviruses; virus-induced immunopathogenesis.

Conflict of interest statement

The authors declare no conflicts of interest

Figures

Figure 1
Figure 1
Dendritic cells (DCs) as “fire accelerants” in hantavirus-induced pathogenesis. (1) After inhalation, pathogenic hantaviruses may productively infect DC subsets in close contact with the respiratory epithelium/alveolar interstitium, thereby inducing DC maturation and migration. (2) Hantavirus-infected DCs can act as shuttles that safely transport virions to endothelial cells (ECs), the main arena of hantavirus-induced pathogenesis, resulting in vascular leakage, and lymphoid tissue, where immune cells are activated. (3) Hantaviruses-infected DCs cause massive bystander activation of immune cells (CD8+ T cells, B cells, NK cells). Bystander-activated immune cells may in turn license DCs cross-presenting hantaviral antigen to initiate powerful hantavirus-specific adaptive immune responses. (4) Both bystander-activated cells and hantavirus-specific immune cells may further aggravate vascular damage by attacking ECs not protected by expression of inhibitory molecules such as PD-L1 or by secreting cytokines that enhance vascular permeability (e.g., IFN-γ).

Similar articles

See all similar articles

References

    1. Steinman R.M., Cohn Z.A. Identification of a novel cell type in peripheral lymphoid organs of mice: I. Morphology, quantitation, tissue distribution. J. Exp. Med. 1973;137:1142–1162. doi: 10.1084/jem.137.5.1142. - DOI - PMC - PubMed
    1. Steinman R.M. Decisions about dendritic cells: past, present, and future. Annu. Rev. Immunol. 2012;30:1–22. doi: 10.1146/annurev-immunol-100311-102839. - DOI - PubMed
    1. Nussenzweig M.C., Mellman I. Ralph Steinman (1943–2011) Nature. 2011;478:460. doi: 10.1038/478460a. - DOI - PubMed
    1. Guilliams M., Ginhoux F., Jakubzick C., Naik S.H., Onai N., Schraml B.U., Segura E., Tussiwand R., Yona S. Dendritic cells, monocytes and macrophages: A unified nomenclature based on ontogeny. Nat. Rev. Immunol. 2014;14:571–578. doi: 10.1038/nri3712. - DOI - PMC - PubMed
    1. Basler C.F. Molecular pathogenesis of viral hemorrhagic fever. Semin. Immunopathol. 2017;39:551–561. doi: 10.1007/s00281-017-0637-x. - DOI - PMC - PubMed
Feedback