3-3- Macrophages and dendritic cells
Mucosal immune responses against infectious agents are orchestrated and regulated by myeloid cells with specialized functions, which include conventional dendritic cells (cDCs), monocyte derived DCs (moDCs), plasmacytoid DCs (pDCs), and macrophages (Guilliams, Lambrecht, & Hammad, 2013). A growing body of evidence points to dysregulated myeloid responses that potentially drive the COVID-19 hallmark syndromes, such as ARDS, CRS and lymphopenia (Mehta et al., 2020).
MERS-CoV infects and replicates inside macrophages and subsequently induces the expression of major histocompatibility complex class I molecules (MHC-I), MHCII, and stimulation-related genes (J. Zhou et al., 2014). Some researchers have reported the great impact of the MERS-CoV spike glycoprotein on the responsiveness of macrophages and monocytes (THP-1 cells) via Toll-like receptors 4 (TLR-4) signaling pathways (Al-Qahtani et al., 2017). Due to homeostasis, macrophage and DC as vehicles seemed to disseminate viruses through the efferent lymphatic system. Meanwhile, activation of DC and macrophage by SARS-CoV led to excessive pro-inflammatory cytokine responses (Tseng, Perrone, Zhu, Makino, & Peters, 2005).
The studies performed on the pulmonary tissues of patients with severe COVID-19 disease have revealed an expansion of inflammatory monocytes and Ficolin-1+ monocyte-derived macrophages at the expense of tissue-resident reparative alveolar macrophages (AMs) (Liao et al., 2020). Additionally, YM1+ FIZZ1+ alternative macrophages can increase airway hypersensitivity, thus exacerbating SARS-associated fibrosis (Page et al., 2012). It seems the role of lung-resident and recruited granulocytes in SARSCoV-2 control and pathogenesis is pivotal (Camp & Jonsson, 2017; ”Eosinophils and Respiratory Viruses,” 2019). In contrast to their early protective role, neutrophil NETosis and macrophage crosstalk can drive later-stage inflammatory cascades (Barnes et al., 2020), underscoring the overall pathogenic nature of the damage-sensing host responses. Evidence reveals that high levels of macrophages chemoattractant Chemokine (C–X–C motif) ligand (CXCL)10/IP-10 and CCL2/MCP-1 and neutrophil chemoattractant CXCL2 and CXCL8 facilitate the migration of these immune cells to the site of infection, which is consistent with the reported mononuclear cell infiltration in lung tissues of COVID-19 patients (Z. Xu et al., 2020).