Innate Immune Components that Regulate the Pathogenesis and Resolution of hRSV and hMPV Infections

Abstract

The human respiratory syncytial virus (hRSV) and human Metapneumovirus (hMPV) are two of the leading etiological agents of acute lower respiratory tract infections, which constitute the main cause of mortality in infants. However, there are currently approved vaccines for neither hRSV nor hMPV. Moreover, despite the similarity between the pathology caused by both viruses, the immune response elicited by the host is different in each case. In this review, we discuss how dendritic cells, alveolar macrophages, neutrophils, eosinophils, natural killer cells, innate lymphoid cells, and the complement system regulate both pathogenesis and the resolution of hRSV and hMPV infections. The roles that these cells play during infections by either of these viruses will help us to better understand the illnesses they cause. We also discuss several controversial findings, relative to some of these innate immune components. To better understand the inflammation in the lungs, the role of the respiratory epithelium in the recruitment of innate immune cells is briefly discussed. Finally, we review the main prophylactic strategies and current vaccine candidates against both hRSV and hMPV.

Keywords: hMPV; hRSV; immunotherapy; innate immune response; vaccines.

Figure 1

Innate immune response elicited upon hRSV infection. Following the detection of hRSV, various types of immune cells are recruited to the lung. Within the innate immune cells, Dendritic cells (DCs), Alveolar Macrophages (AMs), Neutrophils (Neu), Eosinophils (Eos), Natural Killer cells (NK), and Group 2 Innate Lymphoid Cells (ILC2s) can be found. Accordingly, the fixation and activation of the Complement System is detected. Most of these components play a role in the pathology of the infection. The role of the respiratory epithelium in the recruitment of innate immune cells can also be appreciated. Components shaded in blue are elements that contribute to hRSV disease-resolving, whereas components shaded in red are considered detrimental and contribute to hRSV pathogenesis overall. Elements depicted in yellow are those whose contributions to hRSV pathology are not well studied or are controversial. The arrows indicate the possible targets of infection.

Figure 2

Innate immune response elicited upon hMPV infection. After the detection of hMPV, various types of immune cells are recruited to the lung. Within the innate immune cells, Dendritic cells (DCs), Alveolar Macrophages (AMs), Neutrophils (Neu), Eosinophils (Eos), and Natural Killer cells (NK) can be found. Most of these cells play a role in the pathology of the infection. However, Group 2 Innate Lymphoid Cells 2 (ILC2s) and the role of the Complement System during the infection have not been reported yet, and this lack of information is illustrated with “?” in the figure. The role of the respiratory epithelium in the recruitment of innate immune cells can also be appreciated. Components shaded in blue are elements that contribute to hMPV disease resolving, whereas components shaded in red are considered detrimental and contribute to hMPV pathogenesis overall. Elements shaded in yellow are those whose contributions to hMPV pathology are not well studied or are controversial. The arrows indicate the possible targets of infection.