Dendritic Cells in Human Pneumovirus and Metapneumovirus Infections

Abstract

Lung dendritic cells (DC) play a fundamental role in sensing invading pathogens, as well as in the control of tolerogenic responses in the respiratory tract. Their strategic localization at the site of pathogen entry makes them particularly susceptible to initial viral invasion. Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) belong to the Paramyxoviridae family, within the Pneumovirus and Metapneumovirus genera, respectively. hRSV and hMPV are significant human respiratory pathogens that cause similar clinical manifestations and affect many of the same subpopulations. However, they differentially activate the host immune response, including DC, which represents a fundamental link between the innate and adaptive immune response. In this review, the role of DC in the immune response against hRSV and hMPV infections, as well as the inhibitory effects of these paramyxoviruses on the DC immunity will be discussed.

Cell-Mediated Responses to Human Metapneumovirus Infection

“…Respiratory tract DCs are present within the airway epithelium, submucosa, and lung parenchymal tissue under normal, resting conditions. They are highly likely to encounter virions because of their strategic location at the site of virus entry where they can sample antigens throughout the upper and lower respiratory tracts [114]. Upon infection, DCs can be activated directly by the virus through PRRs or indirectly by pro-inflammatory chemokines and cytokines released by AECs or other resident immune cells [115].…”

“…The initiation of the immune response via the secretion of IFNs, chemokines, and other cytokines but also the upregulation of a variety of costimulatory molecules and receptors or cell maturation is crucial for priming virus-specific CD4+ T cells and to initiate the antiviral response. Two groups have shown that hMPV can infect both cDCs and pDCs [49,114,116,117]. Although hMPV infection of DCs results in the expression of viral proteins, no major cytopathic effects such as syncytia formation or massive apoptosis were observed [49].…”

“…Despite the fact that hMPV-infected DCs showed a mild upregulation of co-stimulatory molecules on their surface, they fail to activate specific naïve T cells efficiently [114,122,123]. Priming of hMPV-specific CD4+ T cells by DCs is a critical process in the induction of an antiviral response so naturally, hMPV seems to have developed several mechanisms to impair these functions of DCs [116,123].…”

Interferon-Mediated Response to Human Metapneumovirus Infection

“…Several studies have shown that infection with different strains of HMPV induce a strong immune response characterized by production of interferons in vitro [ 57 , 86 , 87 , 88 , 89 ] or in vivo [ 57 , 88 , 90 , 91 , 92 , 93 ] ( Table 1 ). However, this response is contingent on viral replication as IFN induction is abolished in UV-inactivated HMPV infected cells [ 57 , 94 , 95 ] and in vivo [ 90 ].…”

Immune Response to Human Metapneumovirus Infection: What We Have Learned from the Mouse Model

“…DC have been reported to participate in the innate and adaptive immune response to hMPV infections, indicating their critical role in the antiviral immunity to this virus. Dendritic cells are susceptible to hMPV infection in vitro [ 64 ] and in vivo [ 40 , 65 ]. In fact, hMPV activates mouse lung DC, and induces the upregulation of costimulatory molecules and the secretion of several cytokines including IL-6, IFN-α, IFN-β and TNF-α [ 40 ].…”