scholarly journals There Is Strength in Numbers: Quantitation of Fc Gamma Receptors on Murine Tissue-Resident Macrophages

2021 ◽  
Vol 22 (22) ◽  
pp. 12172
Author(s):  
Christof Vorsatz ◽  
Niklas Friedrich ◽  
Falk Nimmerjahn ◽  
Markus Biburger

Many of the effector functions of antibodies rely on the binding of antibodies/immune complexes to cellular Fcγ receptors (FcγRs). Since the majority of innate immune effector cells express both activating and inhibitory Fc receptors, the outcome of the binding of immune complexes to cells of a given population is influenced by the relative affinities of the respective IgG subclasses to these receptors, as well as by the numbers of activating and inhibitory FcγRs on the cell surface. A group of immune cells that has come into focus more recently is the various subsets of tissue-resident macrophages. The central functions of FcγRs on tissue macrophages include the clearance of opsonized pathogens, the removal of small immune complexes from the circulation and the depletion of antibody-opsonized cells in the therapy of autoimmunity and cancer. Despite these essential functions of FcγRs on tissue-resident macrophages, an in-depth quantification of FcγRs is lacking. Thus, the aim of our current study was to quantify the various Fcγ receptors on macrophages in murine liver, lung, kidney, brain, skin and spleen. Our study identified a pronounced heterogeneity between FcγR expression patterns of the different tissue macrophages, which may reflect their specialized functions within their unique niches in different organ environments.

2021 ◽  
Vol 12 ◽  
Author(s):  
Yijia Li ◽  
Yangzhe Wu ◽  
Yi Hu

Cellular metabolism of both cancer and immune cells in the acidic, hypoxic, and nutrient-depleted tumor microenvironment (TME) has attracted increasing attention in recent years. Accumulating evidence has shown that cancer cells in TME could outcompete immune cells for nutrients and at the same time, producing inhibitory products that suppress immune effector cell functions. Recent progress revealed that metabolites in the TME could dysregulate gene expression patterns in the differentiation, proliferation, and activation of immune effector cells by interfering with the epigenetic programs and signal transduction networks. Nevertheless, encouraging studies indicated that metabolic plasticity and heterogeneity between cancer and immune effector cells could provide us the opportunity to discover and target the metabolic vulnerabilities of cancer cells while potentiating the anti-tumor functions of immune effector cells. In this review, we will discuss the metabolic impacts on the immune effector cells in TME and explore the therapeutic opportunities for metabolically enhanced immunotherapy.


2019 ◽  
Author(s):  
Shirin Kalyan ◽  
Mark Bazett ◽  
Ho Pan Sham ◽  
Momir Bosiljcic ◽  
Beryl Luk ◽  
...  

ABSTRACTRecent developments in understanding how the functional phenotype of the innate immune system is programmed has led to paradigm-shifting views on immunomodulation. These advances have overturned two long-held dogmas: only adaptive immunity confers immunological memory and innate immunity lacks specificity. This work describes the novel observation that innate immune effector cells can be recruited to specific tissues of the body where pathology is present by using a microbial-based immune stimulus that consists of an inactivated pathogen that typically resides or causes infection in that target tissue site. We demonstrate this principle using experimental models of cancer and infection for which different subcutaneously delivered microbial-based treatments were shown to induce the recruitment of immune effector cells to specific diseased organs. Amelioration of disease in a given organ niche was dependent on matching the correct microbial stimulus for the affected organ site but was independent of the nature of the pathology. This observation intriguingly suggests that the immune system, upon pathogen recognition, tends to direct its resources to the compartment in which the pathogen has previously been encountered and would be the most likely source of infection. Importantly, this phenomenon provides a novel means to therapeutically target innate immune effector cells to sites of specific disease localization to potentially treat a wide spectrum of pathologies, including cancer, infection, and chronic inflammatory disorders.AUTHOR SUMMARYVaccines that target adaptive immune memory have revolutionized medicine. This study describes a novel strategy that works as a modified innate immune “vaccine” that exploits the trained response of innate immune effector cells to clear pathology in a specific tissue site. Unlike memory of the adaptive immune system, which functions like a lock and key, innate immune memory is more akin to a reflex response – like experienced muscle or neural cells that are changed by a stimulus to respond more efficiently upon re-exposure. This change in behavior through experience is the definition of learning. Our study suggests that this innate immune learning occurs at different levels. Emergency hematopoiesis trains new innate immune cells in the bone marrow to respond quickly and effectively to a non-specific threat; whereas, pathogen-specific training occurs at sites where cells making up the immunologic niche have had interactions with a particular pathogen and have been trained to respond more robustly to it upon re-presentation in the context of a danger signal. The speed with which new immune cells are trained in the bone marrow in response to an imminent microbial threat and their subsequent recruitment to the target organ site where that microbe typically resides suggests there are ways the immune system communicates to coordinate this rapid response that are yet to be fully delineated. These findings provide a novel highly proficient way to harness the potent effector functions of the innate immune system to address a wide range of immune-based diseases.


PROTEOMICS ◽  
2011 ◽  
Vol 11 (17) ◽  
pp. 3587-3592 ◽  
Author(s):  
Catarina F. Franco ◽  
Romana Santos ◽  
Ana V. Coelho

2001 ◽  
Vol 22 (6) ◽  
pp. 300-301 ◽  
Author(s):  
Jacques Zimmer ◽  
Huguette Bausinger ◽  
Henri de la Salle

Vaccines ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 84 ◽  
Author(s):  
Stephen M Todryk

Most immune responses associated with vaccination are controlled by specific T cells of a CD4+ helper phenotype which mediate the generation of effector antibodies, cytotoxic T lymphocytes (CTLs), or the activation of innate immune effector cells. A rapidly growing understanding of the generation, maintenance, activity, and measurement of such T cells is leading to vaccination strategies with greater efficacy and potentially greater microbial coverage.


2017 ◽  
Vol 13 (3) ◽  
pp. 909-920 ◽  
Author(s):  
Lorena P. Suarez-Kelly ◽  
Amanda R. Campbell ◽  
Isaac V. Rampersaud ◽  
Ambika Bumb ◽  
Min S. Wang ◽  
...  

2001 ◽  
Vol 22 (6) ◽  
pp. 301
Author(s):  
Fu-Dong Shi ◽  
Nora Sarvetnick ◽  
Hans-Gustaf Ljunggren

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