Influenza A virus interactions with macrophages: Lessons from epithelial cells

Abstract

Influenza viruses are an important cause of respiratory infection worldwide. In humans, infection with seasonal influenza A virus (IAV) is generally restricted to the respiratory tract where productive infection of airway epithelial cells promotes viral amplification, dissemination, and disease. Alveolar macrophages (MΦ) are also among the first cells to detect and respond to IAV, where they play a pivotal role in mounting effective innate immune responses. In contrast to epithelial cells, IAV infection of MΦ is a “dead end” for most seasonal strains, where replication is abortive and newly synthesised virions are not released. Although the key replicative stages leading to productive IAV infection in epithelial cells are defined, there is limited knowledge about the abortive IAV life cycle in MΦ. In this review, we will explore host factors and viral elements that support the early stages (entry) through to the late stages (viral egress) of IAV replication in epithelial cells. Similarities, differences, and unknowns for each key stage of the IAV replicative cycle in MΦ will then be highlighted. Herein, we provide mechanistic insights into MΦ‐specific control of seasonal IAV replication through abortive infection, which may in turn, contribute to effective host defence.

COVID-19: The Emerging Immunopathological Determinants for Recovery or Death

“…Previous studies on SARS-CoV suggest low replication in these cells, probably due to phagocytosis (Yilla et al, 2005). Thus, these results suggest that AMs' response to SARS-CoV-2 may be complicated but necessary for the activation and recruitment of other innate cells like monocytes, dendritic cells, neutrophils, natural killer (NK) cells, and essential in the regulation of the adaptive immune system (Soroosh et al, 2013;Hartwig et al, 2014;Meischel et al, 2020).…”

TLR2-mediated activation of innate responses in the upper airways confers antiviral protection of the lungs

“…These results suggest that they are recruited in response to INNA-X-mediated cytokine production to regulate excessive inflammation and limit tissue damage. Their elevated presence at the site of infection nonetheless still contributes to protection as a proportion of these macrophages expressed intracellular viral protein indicating that they had been infected abortively (26,27) and/or that they have phagocytosed apoptotic virus-infected cells (29), serving to limit viral replication (38)(39)(40) before too many rounds of amplification have taken place.…”

“…In addition, significantly greater numbers of NP + macrophages but not neutrophils were detected in nasal tissues of infected INNA-X-treated mice ( Fig 6C) compared to mice treated with diluent and challenged with virus. Macrophages abortively infected by seasonal influenza virus (26,27) can act as a "sink" for virus (28). This, together with their ability to limit infection through the phagocytosis of apoptotic-virus infected cells (29) may explain the presence of intracellular NP and highlights the contribution of macrophages to INNA-Xmediated protection of the nasal epithelium.…”

Porcine Reproductive and Respiratory Syndrome Virus Interferes with Swine Influenza A Virus Infection of Epithelial Cells

“…We thus propose that the balance between these phenomena might explain the discrepancies observed between different in vivo coinfection experiments, for which PRRSV primary infection increases, decreases or has no impact on swIAV co/superinfections. Finally, it is also known that swIAV infects unproductively alveolar macrophages (for review see [61]), the main target of PRRSV, which raises the possibility of a reverse interference of swIAV on PRRSV replication, adding another level of complexity in the interactions between these two viruses.…”