New Review Article Discussing Complement-Targeted Immunotherapy to Fight COVID-19 Infection

Jörg Köhl (University of Lübeck) and Sonata Jodele (Cincinnati Children's Hospital Medical Center) submitted a review article, discussing the role and potential of complement in COVID-19 infection: The complement system is an ancient part of innate immunity sensing highly pathogenic coronaviruses by Mannan-binding lectin resulting in lectin pathway activation and subsequent generation of the anaphylatoxins (AT) C3a and C5a as important effector molecules. Complement deposition in endothelial cells and high blood C5a serum levels have been reported in COVID-19 patients with severe illness, suggesting vigorous complement activation leading to systemic thrombotic microangiopathy (TMA). Strikingly, SARS-CoV-2 infected African Americans suffer from high mortality. Complement regulator gene variants prevalent in African Americans have been associated with a higher risk for severe TMA and multi-organ injury. These findings allow us to apply our knowledge from other complement-mediated diseases to COVID-19 infection to better understand severe disease pathogenesis. 

This review article ‘Tackling COVID-19 infection through complement-targeted immunotherapy’discusses the multiple aspects of complement activation, regulation, crosstalk with other parts of the immune system and the options to target complement in COVID-19 patients to halt disease progression and death. It is currently in the review process in frame of the Themed Issue‘Canonical and non-canonical functions of the complement system in health and disease’ in the British Journal of Pharmacology with Claudia Kemper (University of Lübeck/National Institutes of Health), Ulrich Wenzel (University Hospital Hamburg-Eppendorf) and Jörg Köhl as guest editors. A preprint is already available as a preprint via the online server Authorea.

An Attempt to Polarize Human Neutrophils Toward N1 and N2 Phenotypes in vitro

Research in the past decade revealed a large and hitherto not appreciated phenotypic heterogeneity of neutrophil granulocytes. Especially the tumor-associated N1 and N2 neutrophils that represent immunostimulatory and immunosuppressive subpopulations, respectively, have been subject of intensive research. As most knowledge regarding N1 and N2 neutrophils is derived from murine cancer models, we aimed to develop a model for the phenotypic polarization of human neutrophils in vitro. By providing an activating environment in form of a N1 polarization cocktail or mimicking the tumor environment in form of a N2 polarization cocktail, we were able to drive the polarization of primary human neutrophils in the cell culture toward N1-like and N2-like phenotypes, respectively. Furthermore, we applied our in vitro polarization model to investigate the hypothesis that intracellular pathogens polarize neutrophils toward an immunosuppressive phenotype with limited antimicrobial functions. Indeed, our findings indicate that N2-polarized neutrophils exert a markedly decreased capacity to kill the intracellular parasite Leishmania donovaniand, therefore, promote parasite persistence. Taken together our in vitro polarization model represents a step towards establishing an in vitro protocol for the in-depthanalysis of N1 and N2 neutrophil subsets. For further information please click here