scholarly journals Phagocytosed Polyhedrin-Cytokine Cocrystal Nanoparticles Provide Sustained Secretion of Bioactive Cytokines from Macrophages

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Astrid Wendler ◽  
Nicholas James ◽  
Michael H. Jones ◽  
Christian Pernstich
Keyword(s):  
Drug Delivery ◽  
Wound Healing ◽  
Immune Responses ◽  
Tissue Homeostasis ◽  
Potential Utility ◽  
Active Process ◽  
Phagocytic Cells ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Monocytes And Macrophages

Many cells possess the ability to engulf and incorporate particles by phagocytosis. This active process is characteristic of microorganisms as well as higher order species. In mammals, monocytes, macrophages, and microglia are among the so-called professional phagocytes. In addition, cells such as fibroblast and chondrocytes are classified as nonprofessional phagocytes. Professional phagocytes play important roles in both the innate and adaptive immune responses, wound healing, and tissue homeostasis. Consequently, these cells are increasingly studied as targets and vectors of therapeutic intervention to treat a range of diseases. Professional phagocytes are notoriously difficult to transfect limiting their study and manipulation. Consequently, efforts have shifted towards the development of nanoparticles to deliver a cargo to phagocytic cells via phagocytosis. However, this approach carries significant technical challenges, particularly for protein cargos. We have focused on the development of nanoscale cocrystalline protein depots, known as PODS®, that contain protein cargos, including cytokines. Here, we show that PODS are readily phagocytosed by nonprofessional as well as professional phagocytic cells and have attributes, such as highly sustained release of cargo, that suggest potential utility for the study and exploitation of phagocytic cells for drug delivery. Monocytes and macrophages that ingest PODS retain normal characteristics including a robust chemotactic response. Moreover, the PODS-cytokine cargo is secreted by the loaded cell at a level sufficient to modulate the behavior of surrounding nonphagocytic cells. The results presented here demonstrate the potential of PODS nanoparticles as a novel molecular tool for the study and manipulation of phagocytic cells and for the development of Trojan horse immunotherapy strategies to treat cancer and other diseases.

scholarly journals Phagocytosed polyhedrin-cytokine co-crystal nanoparticles provide sustained secretion of bioactive cytokines from macrophages

2021 ◽  
Author(s):  
Astrid Wendler ◽  
Nicholas James ◽  
Michael H Jones ◽  
Christian Pernstich
Keyword(s):  
Drug Delivery ◽  
Immune Response ◽  
Wound Healing ◽  
Adaptive Immune Response ◽  
Tissue Homeostasis ◽  
Potential Utility ◽  
Active Process ◽  
Phagocytic Cells ◽  
Adaptive Immune ◽  
Monocytes And Macrophages

AbstractMany cells possess the ability to engulf and incorporate particles by phagocytosis. This active process is characteristic of microorganisms as well as higher order species. In mammals, monocytes, macrophages and microglia are among so-called professional phagocytes. In addition, cells such as fibroblast and chondrocytes are classified as non-professional phagocytes. Professional phagocytes play important roles in both the innate and adaptive immune response, wound healing and tissue homeostasis. Consequently, these cells are increasingly studied as targets and vectors of therapeutic intervention to treat a range of diseases. Professional phagocytes are notoriously difficult to transfect limiting their study and manipulation. Consequently, efforts have shifted towards the development of nanoparticles to deliver a cargo to phagocytic cells via phagocytosis. However, this approach carries significant technical challenges, particularly for protein cargos. We have focused on the development of nanoscale co-crystalline protein depots, known as PODS®, that contain protein cargos, including cytokines. Here, we show that PODS are readily phagocytosed by non-professional as well as professional phagocytic cells and have attributes, such as highly sustained release of cargo, that suggest potential utility for the study and exploitation of phagocytic cells for drug delivery. Monocytes and macrophages that ingest PODS retain normal characteristics including a robust chemotactic response. Moreover, the PODS-cytokine cargo is secreted by the loaded cell at a level sufficient to modulate the behavior of surrounding non-phagocytic cells. The results presented here demonstrate the potential of PODS nanoparticles as a novel molecular tool for the study and manipulation of phagocytic cells and for the development of Trojan horse immunotherapy strategies to treat cancer and other diseases.

scholarly journals Dengue Immunopathogenesis: A Crosstalk between Host and Viral Factors Leading to Disease: PART II - DENV Infection, Adaptive Immune Responses, and NS1 Pathogenesis

2020 ◽  
Author(s):  
Henry Puerta-Guardo ◽  
Scott B. Biering ◽  
Eva Harris ◽  
Norma Pavia-Ruz ◽  
Gonzalo Vázquez-Prokopec ◽  
...  
Keyword(s):  
Immune Responses ◽  
Nonstructural Protein ◽  
Severe Disease ◽  
Critical Role ◽  
Denv Infection ◽  
Severe Dengue ◽  
Adaptive Immune Responses ◽  
Dengue Disease ◽  
Adaptive Immune ◽  
Monocytes And Macrophages

Severe disease is associated with serial infection with DENV of different serotypes. Thus, primary DENV infections normally cause asymptomatic infections, and secondary heterotypic infections with a new DENV serotype potentially increase the risks of developing severe disease. Despite many proposed hypotheses trying to explain it, the exact immunological mechanism leading to severe dengue disease is unknown. In turn, severe manifestations are believed to be a consequence of the combinations of many immunopathogenic mechanisms involving viral and host factors leading to increased pathogenesis and disease. Of these mechanisms, the adaptive immune response has been proposed to play a critical role in the development of severe dengue manifestations. This includes the effect of non-neutralizing but enhancing antibodies produced during primary infections, which results in enhanced-DENV infection of Fc-γ-receptor-expressing cells (e.g. monocytes and macrophages) during DENV heterotypic exposure in a phenomenon called antibody-dependent enhancement (ADE); the increased activation of memory T cells during secondary infections, which has low affinity for the current infecting serotype and high affinity for a past infection with a different serotype known as the original antigenic sin; the unbalanced production of pro-inflammatory cytokines that have a direct effect on vascular endothelial cells resulting in plasma leak in a phenomenon known as cytokine storm; and the excessive activation of the complement system that causes exacerbated inflammatory responses, increasing disease severity. In addition to the adaptive immune responses, a secreted viral factor known as the nonstructural protein 1 (NS1) has been recently proposed as the missing corner piece of the DENV pathogenesis influencing disease. This Part II of the chapter will discuss the interplay between the distinct host adaptive immune responses and viral factors that together contribute to the development of DENV pathogenesis and severe disease.

scholarly journals The Role of the Inflammatory Response in Mediating Functional Recovery Following Composite Tissue Injuries

2021 ◽  
Vol 22 (24) ◽  
pp. 13552
Author(s):  
Naveena B. Janakiram ◽  
Michael S. Valerio ◽  
Stephen M. Goldman ◽  
Christopher L. Dearth
Keyword(s):  
Wound Healing ◽  
Immune Responses ◽  
Immune Cells ◽  
Military Service ◽  
Adaptive Immune Responses ◽  
Impaired Wound Healing ◽  
Composite Tissue ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Tissue Injuries

Composite tissue injuries (CTI) are common among US Military Service members during combat operations, and carry a high potential of morbidity. Furthermore, CTI are often complicated due to an altered wound healing response, resulting in part from a dysregulation of the innate and adaptive immune responses. Unlike normal wound healing, in CTI, disruptions occur in innate immune responses, altering neutrophil functions, macrophage activation and polarization, further impacting the functions of T regulatory cells. Additionally, the biological underpinnings of these unfavorable wound healing conditions are multifactorial, including various processes, such as: ischemia, hypoxia, low nutrient levels, and altered cell metabolic pathways, among others, all of which are thought to trigger anergy in immune cells and destabilize adaptive immune responses. As a result, impaired wound healing is common in CTI. Herein, we review the altered innate and adaptive immune cells and their metabolic status and responses following CTI, and discuss the role a multi-pronged immunomodulatory approach may play in facilitating improved outcomes for afflicted patients.

Comparative Biology of γδ T Cells

2002 ◽  
Vol 85 (4) ◽  
pp. 347-358 ◽  
Author(s):  
Zheng W. Chen
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Γδ T Cells ◽  
Tissue Homeostasis ◽  
Innate Immune ◽  
Comparative Biology ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Biological Features ◽  
Αβ T Cells

Accumulative evidence suggests that resident γδ T cells in epithelia are biologically distinct from systemic γδ T cells in the circulation. Murine resident γδ T cells have innate immune characteristics and play an important role in tissue homeostasis after damages. In contrast, a unique subset of circulating γδ T cells in primates, like αβ T cells, can mount adaptive immune responses in infections. This article compares biological features between resident and circulating γδ T cells.

Autophagy in health and disease. 1. Regulation and significance of autophagy: an overview

2010 ◽  
Vol 298 (4) ◽  
pp. C776-C785 ◽  
Author(s):  
Maryam Mehrpour ◽  
Audrey Esclatine ◽  
Isabelle Beau ◽  
Patrice Codogno
Keyword(s):  
Immune Responses ◽  
Molecular Basis ◽  
Cell Function ◽  
Degradation Pathway ◽  
Tissue Homeostasis ◽  
Cytoplasmic Vacuole ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Health And Disease

Macroautophagy is a vacuolar degradation pathway that terminates in the lysosomal compartment after formation of a cytoplasmic vacuole or autophagosome that engulfs macromolecules and organelles. The identification of ATG (autophagy-related) genes that are involved in the formation of autophagosomes has greatly increased our knowledge of the molecular basis of macroautophagy, and its roles in cell function, which extend far beyond degradation and quality control of the cytoplasm. Macroautophagy, which plays a major role in tissue homeostasis, is now recognized as contributing to innate and adaptive immune responses. Recently, several mediators of apoptosis have been shown to control macroautophagy. Deciphering the cross talk between macroautophagy and apoptosis probably should help increase understanding of the role of macroautophagy in human disease and is likely to be of therapeutic importance.

scholarly journals Mycobacterium tuberculosis PE_PGRS20 and PE_PGRS47 Proteins Inhibit Autophagy by Interaction with Rab1A

mSphere ◽  
2021 ◽  
Author(s):  
Emily J. Strong ◽  
Tony W. Ng ◽  
Steven A. Porcelli ◽  
Sunhee Lee
Keyword(s):  
Infectious Disease ◽  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Cellular Process ◽  
Phagocytic Cells ◽  
Adaptive Immune Responses ◽  
Content Type ◽  
Adaptive Immune ◽  
Intracellular Infections

Tuberculosis is a significant global infectious disease caused by infection of the lungs with Mycobacterium tuberculosis , which then resides and replicates mainly within host phagocytic cells. Autophagy is a complex host cellular process that helps control intracellular infections and enhance innate and adaptive immune responses.

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