Activation of Macrophages by Oligomeric Proteins of Different Size and Origin

Abstract

Activation of macrophages is one of the key processes in generating the immune response against pathogens or misfolded/aggregated otherwise unharmful host's proteins. Antigens and their immune complexes (IC) may shape macrophage phenotype in various directions. Data on the impact of protein structure during inflammation are evident; however, some separate steps of this process involving changes in macrophage phenotype are not fully understood. Our aim was to investigate the phenotype of macrophages after activation with different oligomeric proteins and their IC. We have used amyloid beta (Aβ1–42) that plays a role in neurodegenerative inflammation as a model of host-associated protein and three oligomeric viral antigens as pathogen-associated proteins. Murine cell lines J774, BV-2, and macrophage primary cell culture were treated with oligomeric proteins and their IC. After 48 h, expression of surface markers F4/80, CD68, CD86, and CD206 and secreted cytokines IL-10, IL-12, IL-23, and TNF-α was analysed. Aβ1–42 oligomers stimulated expression of both inflammatory and anti-inflammatory molecules; however, fibrils induced less intense expression of markers investigated as compared to small and large oligomers. Two out of three viral oligomeric proteins induced the inflammatory response of macrophages. Data suggest that macrophage activation pattern depends on the origin, size, and structure of oligomeric proteins.

SARS-CoV-2 spike protein binds to bacterial lipopolysaccharide and boosts proinflammatory activity

“…Together, these experiments conclusively demonstrated that SARS-CoV-2 S protein modulates the aggregation state of LPS, analogously to the effects reported for other LPS-binding proteins such as LBP (Kitchens and Thompson, 2005;Ryu et al, 2017). Further, previous reports indicate that LPS and protein aggregates can be proinflammatory (Mueller et al, 2004;Dalgediene et al, 2018). Moreover, LBP can form aggregates with LPS, particularly at a high LPS/LBP ratio (Kitchens and Thompson, 2005), providing additional links to the present findings with SARS-CoV-2 S protein.…”

SARS-CoV-2 Spike protein binds to bacterial lipopolysaccharide and boosts proinflammatory activity

“…Notably, such aggregates were also induced by lipid A, the core of the LPS molecule, common for endotoxin producing bacteria. Previous reports indicate that both LPS and protein aggregates can be proinflammatory (27,28), and moreover, the well-known LPS-binding protein (LBP) forms proinflammatory aggregates with LPS particularly at a high LPS/LBP ratio (29).…”

Amyloid‐β oligomers in cellular models of Alzheimer’s disease

“…These results are supported by a study using primary macrophages, demonstrating how immune response is dependent on the origin, size, and shape of proteins. In fact, by comparing to Aβ fibrils, AβOs induce in a greater extent the expression of M1‐related markers CD86, IL‐23, and TNF‐α (Dalgediene, Luciunaite, & Zvirbliene, 2018). Results in microglial culture may explain the recent failure of several Aβ immunotherapies.…”