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. 2022 Sep 5;22(10):597–613. doi: 10.1038/s41577-022-00775-4

Fig. 2. Immunopathogenesis of human monkeypox.

Fig. 2

ah | Monkeypox virus (MPXV) might enter the body via the respiratory (panel a) or skin (panel b) route. In the respiratory tract, the virus can infect airway epithelial cells such as ciliated cells. Antigen-presenting cells such as dendritic cells and macrophages (MΦ) are also susceptible to MPXV infection. Upon inoculation in the skin, the virus infects keratinocytes and fibroblasts. Skin-resident immune cells such as Langerhans cells, dendritic cells and macrophages are also targeted. In both scenarios (panels a and b), it is hypothesized that infected antigen-presenting cells travel to nearby draining lymph nodes and facilitate its spread through the lymphatic system (panel c). Direct viral access to the lymphatics has been also speculated. A common feature of human monkeypox is swelling of lymph nodes (lymphadenopathy). The abnormal proliferation and retention of natural killer cells might be one of the causes. Following its spread through lymphoid tissue, MPXV may target other large organs such as the spleen and liver (panel d). Of note, MPXV antigens have been previously been detected in both hepatocytes and Kupffer cells in non-human primate (NHP) models. The viraemia wave could then allow the virus to further spread to distant organs such as the skin and gonads. Recently, MPXV was isolated from semen of infected individuals, highlighting the possibility of sexual transmission (panel e). The infection of skin and mucosae leads to the appearance of infective pustules (panel f) and ulcers (panel g). The latter release high quantities of virus into the saliva, which potentially leads to aerosolized transmission of MPXV (panel h).