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Acquisition of Fc-afucosylation of PfEMP1-specific IgG is age-dependent and associated with clinical protection against malaria.
Nat Commun
January 2025
Centre for translational Medicine and Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Protective immunity to malaria depends on acquisition of parasite-specific antibodies, with Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) being one of the most important target antigens. The effector functions of PfEMP1-specific IgG include inhibition of infected erythrocyte (IE) sequestration and opsonization of IEs for cell-mediated destruction. IgG glycosylation modulates antibody functionality, with increased affinity to FcγRIIIa for IgG lacking fucose in the Fc region (Fc-afucosylation).
View Article and Find Full Text PDFThe Topology of Poly(2-methyl-2-oxazine) Shells on Nanoparticles Determines Their Interaction with Serum and Uptake by Immune Cells.
Biomacromolecules
January 2025
Laboratory for Macromolecular and Organic Chemistry, Department of Chemical Sciences, University of Padova, Padova 35131, Italy.
Cyclic poly(2-methyl-2-oxazine) (-PMOZI) brush shells on Au nanoparticles (NPs) exhibit enhanced stealth properties toward serum and different cell lines compared to their linear PMOZI (-PMOZI) counterparts. While selectively recruiting immunoglobulins, -PMOZI shells reduce overall human serum (HS) protein binding and alter the processing of complement factor 3 (C3) compared to chemically identical linear shells. Polymer cyclization significantly decreases NP uptake by nonphagocytic cells and macrophages in both complement-deficient fetal bovine serum (FBS) and complement-expressing HS, indicating ineffective functional opsonization.
View Article and Find Full Text PDFMechanisms of sterilizing immunity provided by an HIV-1 neutralizing antibody against mucosal infection.
PLoS Pathog
December 2024
University Hospital Erlangen, Institute of Clinical and Molecular Virology, Friedrich-Alexander Universität Erlangen-Nürnberg, Germany.
Broadly neutralizing antibodies (bnAbs) against HIV-1 have been shown to protect from systemic infection. When employing a novel challenge virus that uses HIV-1 Env for entry into target cells during the first replication cycle, but then switches to SIV Env usage, we demonstrated that bnAbs also prevented mucosal infection of the first cells. However, it remained unclear whether antibody Fc-effector functions contribute to this sterilizing immunity.
View Article and Find Full Text PDFPotentiating microglial efferocytosis by MFG-E8 improves survival and neurological outcome after successful cardiopulmonary resuscitation in mice.
Brain Pathol
December 2024
Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Brain injury represents the leading cause of mortality and disability after cardiopulmonary resuscitation (CPR) from cardiac arrest (CA), in which the accumulation of dying cells aggravate tissue injury by releasing proinflammatory intracellular components. Microglia play an essential role in maintaining brain homeostasis via milk fat globule epidermal growth factor 8 (MFG-E8)-opsonized efferocytosis, the engulfment of dying cells and debris. This study investigates whether potentiating microglia efferocytosis by MFG-E8 provides neuroprotection after CA/CPR.
View Article and Find Full Text PDFImmunodominant extracellular loops of Treponema pallidum FadL outer membrane proteins elicit antibodies with opsonic and growth-inhibitory activities.
PLoS Pathog
December 2024
Department of Medicine, UConn Health, Farmington, Connecticut, United States of America.
The global resurgence of syphilis has created a potent stimulus for vaccine development. To identify potentially protective antibodies against Treponema pallidum (TPA), we used Pyrococcus furiosus thioredoxin (PfTrx) to display extracellular loops (ECLs) from three TPA outer membrane protein families (outer membrane factors for efflux pumps, eight-stranded β-barrels, and FadLs) to assess their reactivity with immune rabbit serum (IRS). We identified five immunodominant loops from the FadL orthologs TP0856, TP0858 and TP0865 by immunoblotting and ELISA.
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