Table 2.

Impact of (hydroxy)chloroquine on major immune populations

Immune cell	Antiviral activity	Impact of (hydroxy)CQ
Plasmacytoid dendritic cells (pDC)	In response to viral infection pDCs are activated and produce high levels of IFN‐I. Activated pDCs induce the activation of the adaptive immune response	Inhibits pDC maturation and IFN‐I production
Macrophages	Activated through TLR3 binding of dsRNA, promoting macrophage secretion of pro‐inflammatory cytokines	Reduces TNF‐α, IL‐1β and IL‐6 synthesis
Natural Killer cells	NK cells produce IFN‐γ and TNFα in response to a viral infection. NK‐cells recognize low MHC‐I presentation on virus‐infected cells and release perforin causing lysis of the target cell	Inhibiting the processing of perforin to its active form, consequently reducing NK cell cytotoxicity
CD4 T cells	Upon activation produce IFN‐γ and IL‐4. Regulates B‐ lymphocyte and CTL antiviral responses	Downregulated antigen presentation by MHC, limiting the stimulation of CD4 T‐cells and its expression of CD154
CD8 T cells	Upon activation present cytotoxic activity against viral‐infected cells	Inhibits cytotoxic activity by inhibiting lysosomal release
B Cells	Production of virus‐specific antibodies	Altered endosomal pH modulates antigen presentation, biases selection of naïve antigen‐specific B cells, reducing affinity maturation of previously engaged clones

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