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Nanoparticle-Induced Augmentation of Neutrophils’ Phagocytosis of Bacteria

Despite the power of antibiotics, bacterial infections remain a major killer, due to antibiotic resistance and hosts with dysregulated immune systems. We and others have been developing drug-loaded nanoparticles that home to the sites of infection and inflammation via engineered tropism for neutroph...

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Autores principales: Rubey, Kathryn M., Mukhitov, Alexander R., Nong, Jia, Wu, Jichuan, Krymskaya, Vera P., Myerson, Jacob W., Worthen, G. Scott, Brenner, Jacob S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9289463/
https://www.ncbi.nlm.nih.gov/pubmed/35860017
http://dx.doi.org/10.3389/fphar.2022.923814
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author Rubey, Kathryn M.
Mukhitov, Alexander R.
Nong, Jia
Wu, Jichuan
Krymskaya, Vera P.
Myerson, Jacob W.
Worthen, G. Scott
Brenner, Jacob S.
author_facet Rubey, Kathryn M.
Mukhitov, Alexander R.
Nong, Jia
Wu, Jichuan
Krymskaya, Vera P.
Myerson, Jacob W.
Worthen, G. Scott
Brenner, Jacob S.
author_sort Rubey, Kathryn M.
collection PubMed
description Despite the power of antibiotics, bacterial infections remain a major killer, due to antibiotic resistance and hosts with dysregulated immune systems. We and others have been developing drug-loaded nanoparticles that home to the sites of infection and inflammation via engineered tropism for neutrophils, the first-responder leukocytes in bacterial infections. Here, we examined how a member of a broad class of neutrophil-tropic nanoparticles affects neutrophil behavior, specifically questioning whether the nanoparticles attenuate an important function, bacterial phagocytosis. We found these nanoparticles actually augment phagocytosis of non-opsonized bacteria, increasing it by ∼50%. We showed this augmentation of phagocytosis is likely co-opting an evolved response, as opsonized bacteria also augment phagocytosis of non-opsonized bacteria. Enhancing phagocytosis of non-opsonized bacteria may prove particularly beneficial in two clinical situations: in hypocomplementemic patients (meaning low levels of the main bacterial opsonins, complement proteins, seen in conditions such as neonatal sepsis and liver failure) or for bacteria that are largely resistant to complement opsonization (e.g., Neisseria). Additionally, we observe that; 1) prior treatment with bacteria augments neutrophil uptake of neutrophil-tropic nanoparticles; 2) neutrophil-tropic nanoparticles colocalize with bacteria inside of neutrophils. The observation that neutrophil-tropic nanoparticles enhance neutrophil phagocytosis and localize with bacteria inside neutrophils suggests that these nanoparticles will serve as useful carriers for drugs to ameliorate bacterial diseases.
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spelling pubmed-92894632022-07-19 Nanoparticle-Induced Augmentation of Neutrophils’ Phagocytosis of Bacteria Rubey, Kathryn M. Mukhitov, Alexander R. Nong, Jia Wu, Jichuan Krymskaya, Vera P. Myerson, Jacob W. Worthen, G. Scott Brenner, Jacob S. Front Pharmacol Pharmacology Despite the power of antibiotics, bacterial infections remain a major killer, due to antibiotic resistance and hosts with dysregulated immune systems. We and others have been developing drug-loaded nanoparticles that home to the sites of infection and inflammation via engineered tropism for neutrophils, the first-responder leukocytes in bacterial infections. Here, we examined how a member of a broad class of neutrophil-tropic nanoparticles affects neutrophil behavior, specifically questioning whether the nanoparticles attenuate an important function, bacterial phagocytosis. We found these nanoparticles actually augment phagocytosis of non-opsonized bacteria, increasing it by ∼50%. We showed this augmentation of phagocytosis is likely co-opting an evolved response, as opsonized bacteria also augment phagocytosis of non-opsonized bacteria. Enhancing phagocytosis of non-opsonized bacteria may prove particularly beneficial in two clinical situations: in hypocomplementemic patients (meaning low levels of the main bacterial opsonins, complement proteins, seen in conditions such as neonatal sepsis and liver failure) or for bacteria that are largely resistant to complement opsonization (e.g., Neisseria). Additionally, we observe that; 1) prior treatment with bacteria augments neutrophil uptake of neutrophil-tropic nanoparticles; 2) neutrophil-tropic nanoparticles colocalize with bacteria inside of neutrophils. The observation that neutrophil-tropic nanoparticles enhance neutrophil phagocytosis and localize with bacteria inside neutrophils suggests that these nanoparticles will serve as useful carriers for drugs to ameliorate bacterial diseases. Frontiers Media S.A. 2022-07-04 /pmc/articles/PMC9289463/ /pubmed/35860017 http://dx.doi.org/10.3389/fphar.2022.923814 Text en Copyright © 2022 Rubey, Mukhitov, Nong, Wu, Krymskaya, Myerson, Worthen and Brenner. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Rubey, Kathryn M.
Mukhitov, Alexander R.
Nong, Jia
Wu, Jichuan
Krymskaya, Vera P.
Myerson, Jacob W.
Worthen, G. Scott
Brenner, Jacob S.
Nanoparticle-Induced Augmentation of Neutrophils’ Phagocytosis of Bacteria
title Nanoparticle-Induced Augmentation of Neutrophils’ Phagocytosis of Bacteria
title_full Nanoparticle-Induced Augmentation of Neutrophils’ Phagocytosis of Bacteria
title_fullStr Nanoparticle-Induced Augmentation of Neutrophils’ Phagocytosis of Bacteria
title_full_unstemmed Nanoparticle-Induced Augmentation of Neutrophils’ Phagocytosis of Bacteria
title_short Nanoparticle-Induced Augmentation of Neutrophils’ Phagocytosis of Bacteria
title_sort nanoparticle-induced augmentation of neutrophils’ phagocytosis of bacteria
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9289463/
https://www.ncbi.nlm.nih.gov/pubmed/35860017
http://dx.doi.org/10.3389/fphar.2022.923814
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