Respiratory Mononuclear Phagocytes in Human Influenza A Virus Infection: Their Role in Immune Protection and As Targets of the Virus

Abstract

Emerging viruses have become increasingly important with recurrent epidemics. Influenza A virus (IAV), a respiratory virus displaying continuous re-emergence, contributes significantly to global morbidity and mortality, especially in young children, immunocompromised, and elderly people. IAV infection is typically confined to the airways and the virus replicates in respiratory epithelial cells but can also infect resident immune cells. Clearance of infection requires virus-specific adaptive immune responses that depend on early and efficient innate immune responses against IAV. Mononuclear phagocytes (MNPs), comprising monocytes, dendritic cells, and macrophages, have common but also unique features. In addition to being professional antigen-presenting cells, MNPs mediate leukocyte recruitment, sense and phagocytose pathogens, regulate inflammation, and shape immune responses. The immune protection mediated by MNPs can be compromised during IAV infection when the cells are also targeted by the virus, leading to impaired cytokine responses and altered interactions with other immune cells. Furthermore, it is becoming increasingly clear that immune cells differ depending on their anatomical location and that it is important to study them where they are expected to exert their function. Defining tissue-resident MNP distribution, phenotype, and function during acute and convalescent human IAV infection can offer valuable insights into understanding how MNPs maintain the fine balance required to protect against infections that the cells are themselves susceptible to. In this review, we delineate the role of MNPs in the human respiratory tract during IAV infection both in mediating immune protection and as targets of the virus.

Influenza A Virus Inhibits RSV Infection via a Two-Wave Expression of IFIT Proteins

“…Respiratory syncytial virus (RSV) and influenza viruses are two respiratory viruses associated with significant morbidity and mortality worldwide [ 1 ]. RSV is a leading pathogen causing acute lower respiratory tract infection (ALRTI) [ 2 ] in all age groups [ 3 , 4 ], primarily infants and young toddlers [ 5 , 6 ], while the influenza virus affects all age groups [ 7 ]. In Israel, RSV is usually detected in October, with a clear peak in December, whereas the influenza virus arrives in November and peaks in January [ 8 ].…”

Dynamic metabolic reprogramming in dendritic cells: An early response to influenza infection that is essential for effector function

“…To determine if these metabolic pathways were relevant in vivo, we intranasally infected C57BL/6 mice with IAV or mock for 9 days and isolated TNF-α and inducible nitric oxide synthase producing DCs (TipDC) by sorting on CD11b hi , Ly6c/GR-1 hi , MHCII hi surface markers. TipDC are an inflammatory subtype that drive Th1 response and, in the context of IAV infected mice, they present antigen to CD8 T cells and are required for influenza-specific CD8+ T cell proliferation in the lung to mediate viral clearance [91][92][93][94][95]. We purified RNA from TipDC and confidently identified 13,285 transcripts (Tab A in S1 Table).…”

Influenza virus inhibits respiratory syncytial virus (RSV) infection via a two-wave expression of interferon-induced protein with tetratricopeptide (IFIT) proteins

“…2.5-week-old Balb/c mice were anesthetized with isoflurane (Piramal Critical Care, Inhalation liquid) and intranasally infected with influenza A/PR/8/1934 ("influenza PR8") (4x10 PFU/ml). The mice were split into groups according the days of post influenza A/PR/8/1934 infection (1,2,3,5,6,8,10,12), three mice from each group were subsequently infected with RSV (6x10 6 PFU/ml) for 4 days and then sacrificed. The presence of the viruses was tested by grinding the lungs of the mice in 1ml DMEM (Biological Industries, Israel) using the Spex centri prep 8000-D Mixer Mill homogenizer (BENCHMARK SCIENTIFIC), for 10 min, followed by RNA extraction and qRT-PCR, as described (8) and was compared to control mice (mice whom infected with a single virus; RSV only).…”

“…Respiratory syncytial virus (RSV) and influenza viruses are both respiratory viruses associated with significant morbidity and mortality worldwide (1). RSV is a leading pathogen causing acute lower respiratory tract infection (ALRTI) (2) in all age groups (3,4) primarily infants and young toddlers (5,6), while influenza virus affect all age groups (7). In Israel, RSV is usually detected in October, with a clear peak in December, whereas influenza virus arrives in November and peaks in January (8).…”