Microphages activation via antibody-dependent enhancement
A growing body of evidence suggests the host’s innate immune response to SARS-COV-2 infection triggers the inflammation cascade that causes severe tissue damage[18]. In select cases COVID-19 is characterized by a cytokine storm resembling that of macrophage activation seen in viral-induced lymphohistiocytosis and haemophagocytosis[19]. SARS-CoV-2 infects macrophages in the lung and other tissues leading to a surge in the production of pro-inflammatory cytokines.
The ACE2-independent pathway of virus entry depends on the expression of Fc receptors on the cellular membrane of the immune cells. Binding of virus-antibody complex to Fc receptors induces cellular endocytosis[17] (Figure 2). The existing SARS- CoV-2 specific antibodies in MIS-C patients may thus promote viral entry into immune cells resulting in immune cell activation and subsequent acute inflammation. The macrophages are activated when the endosomal Toll-like receptors TLR3, TLR7, and TLR8 start sensing viral RNA and induce a downstream cascade of pro-inflammatory cytokines such as TNF and IL-6[17]. The elevated levels of TNF are the leading cause of septic shock, and multi-organ failure may result in myocardial damage and circulatory failure observed in some COVID-9 patients [20]. The local inflammation and accumulation of pathological macrophage populations in the tissues could be among the leading causes of MIS-C syndrome. Further investigation is required to illustrate the role of macrophage populations in MIS-C syndrome.