Lacy-Hulbert, A. | bioRxiv Science

bioRxiv2020

Ctenophore immune cells produce chromatin traps in response to pathogens and NADPH-independent stimulus

The formation of extracellular DNA traps (ETosis) is a first response mechanism by specific immune cells following exposure to microbes 1,2. Initially characterized in vertebrate neutrophils, cells capable of ETosis have been discovered recently in diverse non-vertebrate taxa 3 4-6. To assess the conservation of ETosis between evolutionarily distant non-vertebrate phyla, we observed and quantified ETosis using the model ctenophore Mnemiopsis leidyi and the oyster Crassostrea gigas. Here we report that ctenophores - thought to have diverged very early from the metazoan stem lineage 7-10- possess immune cell types capable of phagocytosis and ETosis. We demonstrate that both Mnemiopsis and Crassostrea immune cells undergo ETosis after exposure to diverse microbes and chemical agents that stimulate ion flux. Our results support ETosis as an evolutionarily ancient metazoan defense against pathogens.

evolutionary biology↗

bioRxiv2020

Apoptotic cells induce CD103 expression and immunoregulatory function in myeloid dendritic cell precursors through integrin αv and TGF-β activation

In the mammalian gut CD103+ve myeloid DCs are known to suppress inflammation threatened by luminal bacteria, but stimuli driving DC precursor differentiation towards this beneficial phenotype are incompletely understood. We isolated CD11+ve DCs from mesenteric lymph nodes (MLNs) of healthy mice; CD103+ve DCs were 8-24 fold more likely than CD103-ve DCs to exhibit extensive of prior phagocytosis of apoptotic intestinal epithelial cells. However, CD103+ve and CD103-ve MLN DCs exhibited similar ex vivo capacity to ingest apoptotic cells, indicating that apoptotic cells might drive immature DC differentiation towards the CD103+ve phenotype. When cultured with apoptotic cells, myeloid DC precursors isolated from murine bone marrow and characterised as lineage-ve CD103-ve, displayed enhanced expression of CD103 and {beta}8 integrin and acquired increased capacity to induce Tregs after 7d in vitro. However, DC precursors isolated from v-tie2 mice lacking v integrins in the myeloid line exhibited reduced binding of apoptotic cells and complete deficiency in the capacity of apoptotic cells and/or latent TGF-{beta}1 to enhance CD103 expression in culture, whereas active TGF-{beta}1 increased DC precursor CD103 expression irrespective of v expression. Fluorescence microscopy revealed clustering of v integrin chains and latent TGF-{beta}1 at points of contact between DC precursors and apoptotic cells. We conclude that myeloid DC precursors can deploy v integrin to orchestrate binding of apoptotic cells, activation of latent TGF-{beta}1 and acquisition of the immunoregulatory CD103+ve {beta}8+ve DC phenotype. This implies that a hitherto unrecognised consequence of apoptotic cell interaction with myeloid phagocytes is programming that prevents inflammation.

immunology↗