Lethal coronavirus pathogenesis in human monocytes and tissue macrophages

Lethal coronavirus pathogenesis in human monocytes and tissue macrophages

  • Chenghao Huang


Human coronaviruses are capable of undermining the innate immune response through macrophages and monocytes. It is capable of infecting immune cells, delaying initial interferon (IFN) response and thereby supporting robust viral replication.

Pathogenesis includes triggering the production of overwhelming pro-inflammatory cytokines, while suppressing the release of anti-inflammatory mediators. The elevated serum cytokines have also been found to contribute to pathological features seen in diseases such as coagulopathy, acute lung injury and multi-organ failure.


Macrophages are a type of white blood cell of the immune system that engulfs and digests cellular debris and foreign substances etc. They play a critical role in innate immunity and help initiate adaptive immunity (1). They possess high plasticity as well, as illustrated below.

Chenghao's article - polarisation M1

  • classically IFN-γ-activated
  • high level of phagocytic activity and secretion of proinflammatory cytokines and chemokines, which induces Th1 activation
  • high antigen presentation capacity


  • alternatively, IL-4-activated
  • modulate Th2 response
  • produces anti-inflammatory mediators
  • promotes Treg response
  • highly endocytic
  • involved in repair mechanisms, homeostasis, metabolic processes and pathogenesis


Chenghao's article

Pathogenesis through monocytes/macrophages

  • Coronavirus enters monocytes and macrophages via antibody-dependent enhancement: anti-Spike protein antibodies forms immune complexes with virion 🡪 mediates attachment with FcγRII (CD32) receptors and complement receptors on immune cells (3)
  • Anti-spike protein antibodies skew macrophage polarization: presence of anti-spike antibodies prior to viral clearance, suppressed wound-healing responses and promoted MCP1 and IL-8 production and proinflammatory monocyte/macrophage recruitment and accumulation (4)
  • Spike (S) protein induce phenotypic conversion of B cells into macrophage-like cells: conversion of B cells to macrophage-like cells, could be mediated by the spike (S) protein of SARS virus, in combination with severe local hypoxia (5)
  • Delayed IFN response (6): NSP7 and NSP15 have both been identified as potential IFN antagonists; Nucleocapsid (N) protein block type I IFN; Membrane (M) protein block IGN-β
  • Cytokine storm (seen in SARS/MERS/SARS 2): High serum levels of pro-inflammatory cytokines (IFN-γ, IL-1, IL-6, IL-12, MCP 1 and TGF β) and chemokines (CCL2, CXCL10, CXCL9, and IL-8) were induced in macrophages


The poster consolidates existing literature surrounding coronavirus pathogenesis, summarizing the virus’ abilities to trigger aberrant immune response via monocytes and macrophages. The virus is capable of infecting immune cells facilitating its dissemination, delay inflammatory response hence allowing robust viral replication, and triggering a cytokine storm leading to severe clinical manifestations. It is relevant in the current pandemic and provides insight into how patients’ immune responses can be skewed leading to various clinical manifestations, as well as provide an opportunity to consider therapeutic options.


  1. Hirayama D et al. The Phagocytic Function of Macrophage-Enforcing Innate Immunity and Tissue Homeostasis. Int J Mol Sci. 2017;19(1):92.
  2. Malik YA. Properties of Coronavirus and SARS-CoV-2. Malays J Pathol. 2020;42(1):3-11.
  3. Wang SF et al. Antibody-dependent SARS coronavirus infection is mediated by antibodies against spike proteins. Biochem Biophys Res Commun. 2014;451(2):208- 14.
  4. Liu L et al. Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection. JCI Insight. 2019;4(4).
  5. Chiang SF et al. SARS spike protein induces phenotypic conversion of human B cells to macrophage-like cells. Mol Immunol. 2010;47(16):2575-86.
  6. Kindler E et al. Interaction of SARS and MERS Coronaviruses with the Antiviral Interferon Response. Adv Virus Res. 2016;96:219-43.