Dual role of erythrocyte complement receptor type 1 in immune complex-mediated macrophage stimulation: Implications for the pathogenesis of Plasmodium falciparum malaria

M. Odera, W. Otieno, C. Adhiambo, J. A. Stoute

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Given the ability of erythrocytes to bind immune complexes (ICs), we postulated that they can serve a dual role during inflammatory or infectious processes. Erythrocytes could restrict stimulation of macrophages by free ICs by binding C3b-opsonized ICs via their complement receptor 1 (CR1). Conversely, IC-loaded erythrocytes could stimulate macrophages to produce proinflammatory cytokines such as tumour necrosis factor (TNF)-α. To test our hypothesis we selected 72 individuals with low, medium or high red cell CR1 expression and determined their IC binding capacity. We tested the in vitro ability of red cells to inhibit IC-mediated stimulation of TNF-α production by macrophages or to stimulate TNF-α production when loaded with ICs. Plain erythrocytes inhibited IC-induced TNF-α production by macrophages and low CR1 expressors showed the lowest inhibitory capacity. IC-loaded erythrocytes stimulated macrophages to release TNF-α, but the effect was not proportional to the CR1 level. These data support our hypothesis that erythrocytes can serve a dual role in regulation of cytokine responses in a setting of IC formation. Our findings suggest that individuals with low CR1 expression are ill-equipped to clear ICs and prevent IC-mediated stimulation of macrophages. In addition, IC-loaded red cells in areas of sluggish circulation such as in the spleen or in brain capillaries blocked by sequestered malaria-infected red cells may induce inflammation by stimulating monocytes and macrophages, the latter leading to the development of cerebral malaria.

Original languageEnglish (US)
Pages (from-to)201-207
Number of pages7
JournalClinical and Experimental Immunology
Volume166
Issue number2
DOIs
StatePublished - Nov 2011

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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