Respiratory Epithelial Cells as Master Communicators during Viral Infections

Abstract

Purpose of review: Communication by epithelial cells during respiratory viral infections is critical in orchestrating effective anti-viral responses but also can lead to excessive inflammation. This review will evaluate studies that investigate how respiratory epithelial cells influence the behavior of immune cells and how epithelial cell/immune cell interactions contribute to antiviral responses and immunopathology outcomes. Recent findings: Previous studies have characterized cytokine responses of virus-infected epithelial cells.More recent studies have carefully demonstrated the effects of these cytokines on cellular behaviors within the infected lung. Infected epithelial cells release exosomes that specifically regulate responses of monocytes and neighboring epithelial cells without promoting spread of virus. In contrast, rhinovirus-infected cells induce monocytes to upregulate expression of the viral receptor, promoting spread of the virus to alternate cell types. The precise alteration of PDL expression on infected epithelial cells has been shown to switch between inhibition and activation of antiviral responses.Summary: These studies have more precisely defined the interactions between epithelial and immune cells during viral infections. This level of understanding is critical for the development of novel therapeutic strategies that promote effective antiviral responses or epithelial repair, or inhibit damaging inflammatory responses during severe respiratory viral infections.

Host–Pathogen Responses to Pandemic Influenza H1N1pdm09 in a Human Respiratory Airway Model

“…The body's natural defense mechanism of inflammation which promotes cell repair and healing [107] was mimicked in our wdNHBE model, with the increased expression of proinflammatory cytokines and chemokines such as TNF, IL1B, IL6, CXCL8 and CXCL10. This suggests that wdNHBE cells recognize IAV and poly(I:C) through binding to pattern recognition receptors (PRRs) such as the Toll-like receptors (TLR3, TLR7, and TLR8), retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein-5 (MDA-5), triggering innate immune response signaling cascades as occurs in vivo [22,54,55,[108][109][110][111][112][113][114]. Antiviral, pro-and anti-inflammatory cytokines and chemokines are then upregulated in the host [27,56,115].…”

Single-cell transcriptomic atlas of primate cardiopulmonary aging

“…The lung epithelium, technically on the outside of the body and lined with 95% of alveolar type I cells (AT1), is highly vulnerable to viral infection. 11 The remaining fraction is made up of alveolar type II cells (AT2), which mediate the synthesis and secretion of pulmonary surfactant, with a subset of cells reported to generate new alveolar cells during lung injury. 12 The lung also consists of capillary cells, mesenchymal cells, and a specialized set of lung-resident immune cells called alveolar macrophages (AMs) and interstitial macrophages (IMs).…”

Extracellular Vesicles in Viral Infections: Two Sides of the Same Coin?

“…Even when envelopes are acquired in canonical pathways, the exosomal pathway can be exploited by viruses to facilitate its own transmission, as seen for porcine reproductive and respiratory syndrome virus (PRRSV) (Wang et al, 2018), herpes simplex virus HSV-1 (Bello-Morales and López-Guerrero, 2020), enterovirus 71 (Gu et al, 2020), and RVFV, which pack viral RNA and proteins inside vesicles (Ahsan et al, 2016); HIV, which facilitates macrophage infection through EVs (Kadiu et al, 2012); HBV, which can directly induce replication through EVs of infected cells ; and HTLV-1, which exports functional viral proteins inside EVs to uninfected cells (Jaworski et al, 2014). Cells infected with rhinovirus secrete EVs that induce the upregulation of viral receptors in monocytes, which allows the virus to infect alternative cell types (Miura, 2019). Mosquito cells infected with DENV secrete larger EVs than uninfected cells, and these structures contain virus-like particles that are able to infect other cells (Reyes-Ruiz et al, 2019).…”

“…EVs facilitate viral transmission HSV-1 (Bello-Morales and López-Guerrero, 2020), KSHV (Chen et al, 2020)., NDV (Zhou C. et al, 2019), PRRSV (Wang et al, 2017), enterovirus 71 (Gu et al, 2020), HCV (Bukong et al, 2014), HIV (Kadiu et al, 2012), SFTS (Silvas et al, 2016) Viral RNAs/proteins inside EVs Coronavirus (Maeda et al, 1999), EBV (Keryer-Bibens et al, 2006), HCV (Kouwaki et al, 2017)., HTLV-1, (Jaworski et al, 2014), RVFV (Ahsan et al, 2016), ZIKV (Zhou W. et al, 2019;Martıńez-Rojas et al, 2020) Infectious virus-like particles/cloaked virions inside EVs DENV (Reyes-Ruiz et al, 2019), enterovirus 71 (Gu et al, 2020), HCV (Bartosch et al, 2003;Timpe et al, 2008) Transfer of infective RNA through EVs withouth complete viral particles HCV (Longatti et al, 2015), FMDV (Zhang et al, 2019), EVs turn cells more permissive to infection, membrane/receptor modulation HIV (Arenaccio et al, 2014;Dubrovsky et al, 2020), Rhinovirus (Miura, 2019) Host molecules in EVs facilitate viral stability and replication in recipient cells HBV , HCV (Bukong et al, 2014;Altan-Bonnet, 2016), HIV (Arenaccio et al, 2014;Ranjit et al, 2020) Amplification of EV production ZIKV (Zhou W. et al, 2019) EVs from uninfected cells can activate latent viruses HIV (Barclay et al, 2020) EVS RELATED TO IMMUNE RESPONSES…”