Search results for "Innate"

Innate and Adaptive Immunity in Aging and Longevity: The Foundation of Resilience

2020

The interrelation of the processes of immunity and senescence now receives an unprecedented emphasis during the COVID-19 pandemic, which brings to the fore the critical need to combat immunosenescence and improve the immune function and resilience of older persons. Here we review the historical origins and the current state of the science of innate and adaptive immunity in aging and longevity. From the modern point of view, innate and adaptive immunity are not only affected by aging but also are important parts of its underlying mechanisms. Excessive levels or activity of antimicrobial peptides, C-reactive protein, complement system, TLR/NF-κB, cGAS/STING/IFN 1,3 and AGEs/RAGE pathways, mye…

ISG15 Is Upregulated in Respiratory Syncytial Virus Infection and Reduces Virus Growth through Protein ISGylation

2016

ABSTRACT Human respiratory syncytial virus (RSV), for which neither a vaccine nor an effective therapeutic treatment is currently available, is the leading cause of severe lower respiratory tract infections in children. Interferon-stimulated gene 15 (ISG15) is a ubiquitin-like protein that is highly increased during viral infections and has been reported to have an antiviral or a proviral activity, depending on the virus. Previous studies from our laboratory demonstrated strong ISG15 upregulation during RSV infection in vitro . In this study, an in-depth analysis of the role of ISG15 in RSV infection is presented. ISG15 overexpression and small interfering RNA (siRNA)-silencing experiments,…

Formyl-peptide receptor 2 governs leukocyte influx in local Staphylococcus aureus infections

2017

Leukocytes express formyl-peptide receptors (FPRs), which sense microbe-associated molecular pattern (MAMP) molecules, leading to leukocyte chemotaxis and activation. We recently demonstrated that phenol-soluble modulin (PSM) peptides from highly pathogenic Staphylococcus aureus are efficient ligands for the human FPR2. How PSM detection by FPR2 impacts on the course of S. aureus infections has remained unknown. We characterized the specificity of mouse FPR2 (mFpr2) using a receptor-transfected cell line, homeobox b8 (Hoxb8), and primary neutrophils isolated from wild-type (WT) or mFpr2−/− mice. The influx of leukocytes into the peritoneum of WT and mFpr2−/− mice was analyzed. We demonstrat…

Mathematical investigation of innate immune responses to lung cancer: The role of macrophages with mixed phenotypes

2021

Abstract Macrophages’ role in the evolution of solid tumours is a well accepted fact, with the M1-like macrophages having an anti-tumour role and the M2-like macrophages having a pro-tumour role. Despite the fact that some clinical studies on lung tumours have emphasised also the presence of macrophages with mixed M1 and M2 phenotypes in addition to macrophages with distinct phenotypes, the majority of studies still use the distinct M1-M2 classification to predict the evolution of tumours and patient survival. In this theoretical study we use a mathematical modelling and computational approach to investigate the role of macrophages with mixed phenotype on growth/control/elimination of lung …

Gut germinal center regeneration and enhanced antiviral immunity by mesenchymal stem/stromal cells in SIV infection.

2021

Although antiretroviral therapy suppresses HIV replication, it does not eliminate viral reservoirs or restore damaged lymphoid tissue, posing obstacles to HIV eradication. Using the SIV model of AIDS, we investigated the effect of mesenchymal stem/stromal cell (MSC) infusions on gut mucosal recovery, antiviral immunity, and viral suppression and determined associated molecular/metabolic signatures. MSC administration to SIV-infected macaques resulted in viral reduction and heightened virus-specific responses. Marked clearance of SIV-positive cells from gut mucosal effector sites was correlated with robust regeneration of germinal centers, restoration of follicular B cells and T follicular h…

Parallels and differences between innate and adaptive lymphocytes.

2016

Lymphocytes are essential in innate and adaptive immunity. Recent insights suggest that some innate lymphocytes execute functions with adaptive characteristics, while adaptive lymphocytes can operate in ways reminiscent of innate cells. Rather than partitioning lymphocytes according to the type of effector function they execute, we propose that a relevant discrimination relates to the existence of conventional T cells in a naive state. The naive state can be seen as an actively repressed condition that supports T cell diversity and enables the flexible differentiation of effector cells in a manner that best addresses the antigenic challenge. We discuss these considerations in the context of…

Guidelines for the use of flow cytometry and cell sorting in immunological studies

2017

The marriage between immunology and cytometry is one of the most stable and productive in the recent history of science. A rapid search in PubMed shows that, as of July 2017, using “flow cytometry immunology” as a search term yields more than 68 000 articles, the first of which, interestingly, is not about lymphocytes. It might be stated that, after a short engagement, the exchange of the wedding rings between immunology and cytometry officially occurred when the idea to link fluorochromes to monoclonal antibodies came about. After this, recognizing different types of cells became relatively easy and feasible not only by using a simple fluorescence microscope, but also by a complex and some…

Bronchial inflammation and bacterial load in stable COPD is associated with TLR4 overexpression.

2017

Toll-like receptors (TLRs) and nucleotide-binding oligomerisation domain (NOD)-like receptors (NLRs) are two major forms of innate immune sensors but their role in the immunopathology of stable chronic obstructive pulmonary disease (COPD) is incompletely studied. Our objective here was to investigate TLR and NLR signalling pathways in the bronchial mucosa in stable COPD.Using immunohistochemistry, the expression levels of TLR2, TLR4, TLR9, NOD1, NOD2, CD14, myeloid differentiation primary response gene 88 (MyD88), Toll-interleukin-1 receptor domain-containing adaptor protein (TIRAP), and the interleukin-1 receptor-associated kinases phospho-IRAK1 and IRAK4 were measured in the bronchial muc…

Activation and selective IL-17 response of human Vγ9Vδ2 T lymphocytes by TLR-activated plasmacytoid dendritic cells.

2016

// Elena Lo Presti 1,2 , Nadia Caccamo 1,2 , Valentina Orlando 1,2 , Francesco Dieli 1,2 and Serena Meraviglia 1,2 1 Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), University of Palermo, Palermo, Italy 2 Department of Biopathology and Medical Biotechnologies (DIBIMED), University of Palermo, Palermo, Italy Correspondence to: Serena Meraviglia, email: // Keywords : γδ T cells, plasmacytoid dendritic cells, IL-17, TLR activation, proliferation, Immunology and Microbiology Section, Immune response, Immunity Received : July 20, 2016 Accepted : August 02, 2016 Published :August 31, 2016 Abstract Vγ9Vδ2 T cells and plasmacytoid dendritic cells (pDCs) are two distinc…

2017

Bruton's tyrosine kinase (BTK) was initially discovered as a critical mediator of B cell receptor signaling in the development and functioning of adaptive immunity. Growing evidence also suggests multiple roles for BTK in mononuclear cells of the innate immune system, especially in dendritic cells and macrophages. For example, BTK has been shown to function in Toll-like receptor-mediated recognition of infectious agents, cellular maturation and recruitment processes, and Fc receptor signaling. Most recently, BTK was additionally identified as a direct regulator of a key innate inflammatory machinery, the NLRP3 inflammasome. BTK has thus attracted interest not only for gaining a more thoroug…