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.