scholarly journals Type 3 muscarinic receptors contribute to intestinal mucosal homeostasis and clearance of Nippostrongylus brasiliensis through induction of TH2 cytokines

2016 ◽  
Vol 311 (1) ◽  
pp. G130-G141 ◽  
Author(s):  
Leon P. McLean ◽  
Allen Smith ◽  
Lumei Cheung ◽  
Joseph F. Urban ◽  
Rex Sun ◽  
...  
Keyword(s):  
Muscarinic Receptors ◽  
Host Defense ◽  
Cell Function ◽  
Immune Cell ◽  
Nippostrongylus Brasiliensis ◽  
Epithelial Secretion ◽  
Mucosal Homeostasis ◽  
Small Intestinal ◽  
Type 3

Despite increased appreciation for the role of nicotinic receptors in the modulation of and response to inflammation, the contribution of muscarinic receptors to mucosal homeostasis, clearance of enteric pathogens, and modulation of immune cell function remains relatively undefined. Uninfected and Nippostrongylus brasiliensis-infected wild-type and type 3 muscarinic receptor (M3R)-deficient ( Chrm3 −/−) mice were studied to determine the contribution of M3R to mucosal homeostasis as well as host defense against the TH2-eliciting enteric nematode N. brasiliensis. Intestinal permeability and expression of TH1/TH17 cytokines were increased in uninfected Chrm3 −/− small intestine. Notably, in Chrm3 −/− mice infected with N. brasiliensis, small intestinal upregulation of TH2 cytokines was attenuated and nematode clearance was delayed. In Chrm3 −/− mice, TH2-dependent changes in small intestinal function including smooth muscle hypercontractility, increased epithelial permeability, decreased epithelial secretion and absorption, and goblet cell expansion were absent despite N. brasiliensis infection. These findings identify an important role for M3R in host defense and clearance of N. brasiliensis, and support the expanding role of cholinergic muscarinic receptors in maintaining mucosal homeostasis.

scholarly journals Polymorphism in BACH2 gene is a marker of polyglandular autoimmunity

Endocrine ◽  
2021 ◽  
Author(s):  
Marta Fichna ◽  
Magdalena Żurawek ◽  
Bartosz Słomiński ◽  
Marta Sumińska ◽  
Agata Czarnywojtek ◽  
...  
Keyword(s):  
Immune Cell ◽  
Premature Menopause ◽  
Complex Disorders ◽  
Increased Risk ◽  
Organ Specific ◽  
Autoimmune Conditions ◽  
Cell Balance ◽  
Type 3 ◽  
Polyglandular Autoimmunity

Abstract Purpose Genetically predisposed individuals may develop several autoimmune diseases—autoimmune polyendocrine syndromes (APS). APS types 2–4, are complex disorders, which combine various organ-specific autoimmune conditions. Recent reports support the considerable role of the BACH2 gene in immune cell differentiation and shifting the T-cell balance towards regulatory T-cells. BACH2 polymorphisms are associated with autoimmune disorders, including Addison’s disease (AD), Graves’ disease (GD), and probably type 1 diabetes (T1D). Our study was aimed to investigate the BACH2 variant, rs3757247, in endocrine autoimmunity in the Polish population. Methods The analysis comprised 346 individuals with APS, 387 with T1D only, and 568 controls. Genotyping was performed using TaqMan chemistry. Results APS type 2 was found in 219 individuals, type 3 in 102, and type 4 in 25 subjects. Overall, AD was diagnosed in 244 subjects, Hashimoto’s thyroiditis—in 238, T1D—in 127, GD—in 58, vitiligo and chronic gastritis each in 40 patients, celiac disease—in 28, premature menopause in 18, and alopecia in 4 patients. Minor T allele at rs3757247 was found in 56.4% APS vs. 44.1% control alleles (OR 1.59; 95%CI: 1.30–1.95, p < 0.0001). The distribution of genotypes revealed excess TT homozygotes in the APS cohort (33.2 vs. 20.1% in controls, p < 0.0001). The frequencies of rs3757247 alleles and genotypes in T1D patients did not present significant differences vs. controls (p-values > 0.05). Conclusions These results provide evidence of the association between BACH2 polymorphism and polyglandular autoimmunity. Since carriers of rs3757247 display increased risk for additional autoimmune conditions, this variant could identify individuals prone to develop APS.

Surfactant protein A protects growing cells and reduces TNF-alpha activity from LPS-stimulated macrophages

1996 ◽  
Vol 271 (2) ◽  
pp. L310-L319 ◽  
Author(s):  
J. C. McIntosh ◽  
S. Mervin-Blake ◽  
E. Conner ◽  
J. R. Wright
Keyword(s):  
Host Defense ◽  
Alveolar Macrophages ◽  
Cell Function ◽  
Immune Cell ◽  
Protein A ◽  
Surfactant Protein ◽  
Alpha Activity ◽  
Tnf Alpha ◽  
Activated Macrophages ◽  
Immune Functions

In addition to its effect on surfactant lipids, surfactant protein (SP)-A promotes host defense. To define further the role of SP-A in regulating immune cell function, we evaluated the effect of SP-A on lipopolysaccharide (LPS)-activated alveolar macrophages in two settings. First, cocultured LPS-activated macrophages significantly inhibited lung fibroblast growth, but SP-A (added daily) attenuated this effect. Both LPS and SP-A acted via macrophages rather than directly on the fibroblasts, at least partially by affecting tumor necrosis factor (TNF)-alpha activity. TNF-alpha reproduced the growth suppression, anti-TNF-alpha antibodies attenuated the effect LPS-activated macrophages, and SP-A reduced TNF-alpha activity in conditioned medium. Second, SP-A reduced TNF-alpha activity in medium from isolated LPS-stimulated macrophages. The effects of SP-A were noted with or without serum, were dose-dependent and reversible, and were seen with two different serotypes of smooth LPS. Equimolar concentrations of immunoglobulin G and C1q had no effect. Thus SP-A both enhances host defense and modulates immune functions of alveolar macrophages.

scholarly journals Impact of Exercise on Immunometabolism in Multiple Sclerosis

2020 ◽  
Vol 9 (9) ◽  
pp. 3038 ◽  
Author(s):  
Remsha Afzal ◽  
Jennifer K Dowling ◽  
Claire E McCoy
Keyword(s):  
Multiple Sclerosis ◽  
Cell Function ◽  
Immune Cell ◽  
Therapeutic Benefits ◽  
Demyelinating Lesions ◽  
Inflammatory State ◽  
Autoimmune Condition ◽  
The Central Nervous System ◽  
Axonal Degradation

Multiple Sclerosis (MS) is a chronic, autoimmune condition characterized by demyelinating lesions and axonal degradation. Even though the cause of MS is heterogeneous, it is known that peripheral immune invasion in the central nervous system (CNS) drives pathology at least in the most common form of MS, relapse-remitting MS (RRMS). The more progressive forms’ mechanisms of action remain more elusive yet an innate immune dysfunction combined with neurodegeneration are likely drivers. Recently, increasing studies have focused on the influence of metabolism in regulating immune cell function. In this regard, exercise has long been known to regulate metabolism, and has emerged as a promising therapy for management of autoimmune disorders. Hence, in this review, we inspect the role of key immunometabolic pathways specifically dysregulated in MS and highlight potential therapeutic benefits of exercise in modulating those pathways to harness an anti-inflammatory state. Finally, we touch upon current challenges and future directions for the field of exercise and immunometabolism in MS.

scholarly journals Maternal Par4 and platelets contribute to defective placenta formation in mouse embryos lacking thrombomodulin

Blood ◽  
2008 ◽  
Vol 112 (3) ◽  
pp. 585-591 ◽  
Author(s):  
Rashmi Sood ◽  
Lynette Sholl ◽  
Berend Isermann ◽  
Mark Zogg ◽  
Shaun R. Coughlin ◽  
...  
Keyword(s):  
Cell Function ◽  
Immune Cell ◽  
Fetal Loss ◽  
Trophoblast Cells ◽  
Protease Activated Receptors ◽  
Genetic Ablation ◽  
Coagulation Inhibitor ◽  
Placental Failure ◽  
New Evidence

Abstract Absence of the blood coagulation inhibitor thrombomodulin (Thbd) from trophoblast cells of the mouse placenta causes a fatal arrest of placental morphogenesis. The pathogenesis of placental failure requires tissue factor, yet is not associated with increased thrombosis and persists in the absence of fibrinogen. Here, we examine the role of alternative targets of coagulation that might contribute to the placental failure and death of Thbd−/− embryos. We demonstrate that genetic deficiency of the protease-activated receptors, Par1 or Par2, in the embryo and trophoblast cells does not prevent the death of Thbd−/− embryos. Similarly, genetic ablation of the complement pathway or of maternal immune cell function does not decrease fetal loss. In contrast, Par4 deficiency of the mother, or the absence of maternal platelets, restores normal development in one-third of Thbd-null embryos. This finding generates new evidence implicating increased procoagulant activity and thrombin generation in the demise of thrombomodulin-null embryos, and suggests that platelets play a more prominent role in placental malfunction associated with the absence of thrombomodulin than fibrin formation. Our findings demonstrate that fetal prothrombotic mutations can cause localized activation of maternal platelets at the feto-maternal interface in a mother with normal hemostatic function.

scholarly journals Altered Ca2+ Homeostasis in Immune Cells during Aging: Role of Ion Channels

2020 ◽  
Vol 22 (1) ◽  
pp. 110
Author(s):  
Dorina Zöphel ◽  
Chantal Hof ◽  
Annette Lis
Keyword(s):  
Immune Cells ◽  
Irreversible Process ◽  
Cell Function ◽  
Immune Cell ◽  
Compensatory Mechanisms ◽  
Cellular Environment ◽  
Age Related ◽  
Dependent Processes ◽  
Equal Density

Aging is an unstoppable process and begins shortly after birth. Each cell of the organism is affected by the irreversible process, not only with equal density but also at varying ages and with different speed. Therefore, aging can also be understood as an adaptation to a continually changing cellular environment. One of these very prominent changes in age affects Ca2+ signaling. Especially immune cells highly rely on Ca2+-dependent processes and a strictly regulated Ca2+ homeostasis. The intricate patterns of impaired immune cell function may represent a deficit or compensatory mechanisms. Besides, altered immune function through Ca2+ signaling can profoundly affect the development of age-related disease. This review attempts to summarize changes in Ca2+ signaling due to channels and receptors in T cells and beyond in the context of aging.

scholarly journals PD-1 blockade exacerbates Mycobacterium tuberculosis infection in rhesus macaques

2021 ◽  
Vol 6 (55) ◽  
pp. eabf3861
Author(s):  
Keith D. Kauffman ◽  
Shunsuke Sakai ◽  
Nickiana E. Lora ◽  
Sivaranjani Namasivayam ◽  
Paul J. Baker ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Cell Function ◽  
Immune Cell ◽  
Rhesus Macaques ◽  
Imaging Studies ◽  
Chronic Infections ◽  
Mycobacterium Tuberculosis Infection ◽  
Cell Responses

Boosting immune cell function by targeting the coinhibitory receptor PD-1 may have applications in the treatment of chronic infections. Here, we examine the role of PD-1 during Mycobacterium tuberculosis (Mtb) infection of rhesus macaques. Animals treated with anti–PD-1 monoclonal antibody developed worse disease and higher granuloma bacterial loads compared with isotype control–treated monkeys. PD-1 blockade increased the number and functionality of granuloma Mtb-specific CD8 T cells. In contrast, Mtb-specific CD4 T cells in anti–PD-1–treated macaques were not increased in number or function in granulomas, expressed increased levels of CTLA-4, and exhibited reduced intralesional trafficking in live imaging studies. In granulomas of anti–PD-1–treated animals, multiple proinflammatory cytokines were elevated, and more cytokines correlated with bacterial loads, leading to the identification of a role for caspase 1 in the exacerbation of tuberculosis after PD-1 blockade. Last, increased Mtb bacterial loads after PD-1 blockade were found to associate with the composition of the intestinal microbiota before infection in individual macaques. Therefore, PD-1–mediated coinhibition is required for control of Mtb infection in macaques, perhaps because of its role in dampening detrimental inflammation and allowing for normal CD4 T cell responses.

scholarly journals Identification of a prostaglandin E2 receptor that regulates mosquito oenocytoid immune cell function in limiting bacteria and parasite infection

2020 ◽  
Author(s):  
Hyeogsun Kwon ◽  
David R. Hall ◽  
Ryan C. Smith
Keyword(s):  
Immune Responses ◽  
Prostaglandin E2 ◽  
Cell Function ◽  
Immune Cell ◽  
Protective Effects ◽  
Immune Cell Function ◽  
Humoral Immune ◽  
High Concentrations ◽  
Prostaglandin E2 Receptor

AbstractLipid-derived signaling molecules known as eicosanoids have integral roles in mediating immune and inflammatory processes across metazoans. This includes the function of prostaglandins and their cognate G protein-coupled receptors (GPCRs) to employ their immunological actions. In insects, prostaglandins have been implicated in the regulation of both cellular and humoral immune responses, yet studies have been limited by the absence of a described prostaglandin receptor. Here, we characterize a prostaglandin E2 receptor (AgPGE2R) in the mosquito Anopheles gambiae and examine its contributions to innate immunity. AgPGE2R expression is most abundant in circulating hemocytes where it is primarily localized to oenocytoid immune cell populations. Through the administration of prostaglandin E2 (PGE2) and AgPGE2R-silencing by RNAi, we demonstrate that PGE2 signaling regulates the expression of a subset of prophenoloxidases (PPOs) and antimicrobial peptides (AMPs). PGE2 priming via the AgPGE2R significantly limited bacterial replication and suppressed Plasmodium oocyst survival. Additional experiments establish that PGE2 priming increases phenoloxidase (PO) activity through the increased expression of PPO1 and PPO3, which significantly influence Plasmodium oocyst survival. We also provide evidence that PGE2 priming is concentration-dependent, where high concentrations of PGE2 promote oenocytoid lysis, negating the protective effects of PGE2 priming on anti-Plasmodium immunity. Taken together, our results characterize the AgPGE2R and the role of prostaglandin signaling on immune cell function, providing new insights into the role of PGE2 on anti-bacterial and anti-Plasmodium immune responses in the mosquito host.

The Role of Fibrin(ogen) in Wound Healing and Infection Control

2021 ◽  
Author(s):  
Katherine J. Kearney ◽  
Robert A.S. Ariëns ◽  
Fraser L. Macrae
Keyword(s):  
Wound Healing ◽  
Bacterial Infection ◽  
Chronic Wounds ◽  
Cell Function ◽  
Immune Cell ◽  
Bacterial Strains ◽  
Dual Roles ◽  
Bacterial Proteins ◽  
Highly Virulent

AbstractFibrinogen, one of the most abundant plasma proteins playing a key role in hemostasis, is an important modulator of wound healing and host defense against microbes. In the current review, we address the role of fibrin(ogen) throughout the process of wound healing and subsequent tissue repair. Initially fibrin(ogen) acts as a provisional matrix supporting incoming leukocytes and acting as reservoir for growth factors. It later goes on to support re-epithelialization, angiogenesis, and fibroplasia. Importantly, removal of fibrin(ogen) from the wound is essential for wound healing to progress. We also discuss how fibrin(ogen) functions through several mechanisms to protect the host against bacterial infection by providing a physical barrier, entrapment of bacteria in fibrin(ogen) networks, and by directing immune cell function. The central role of fibrin(ogen) in defense against bacterial infection has made it a target of bacterial proteins, evolved to interact with fibrin(ogen) to manipulate clot formation and degradation for the purpose of promoting microbial virulence and survival. Further understanding of the dual roles of fibrin(ogen) in wound healing and infection could provide novel means of therapy to improve recovery from surgical or chronic wounds and help to prevent infection from highly virulent bacterial strains, including those resistant to antibiotics.

Role of Regulatory T Cells in Infection and Vaccination During Early Infancy

2018 ◽  
Vol 24 (30) ◽  
pp. 3495-3505
Author(s):  
Samanta C. Funes ◽  
Miguel A. Mansilla ◽  
Gisela Canedo-Marroquín ◽  
Margarita K. Lay ◽  
Claudia A. Riedel ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Active Role ◽  
Treg Cells ◽  
Health Goals ◽  
Inhibitory Mechanisms ◽  
Neonates And Infants

Reducing infant mortality due to infectious diseases is one of the most important public health goals worldwide. Several approaches have been implemented to reach this goal and vaccination has been an effective strategy for reducing infant and newborn mortality. However, the immunological features of neonates and infants represent a significant barrier to the effectiveness of vaccination. Since regulatory T cells (Treg cells) are known to play an active role in contributing to various mechanisms of suppression of the immune cell function. It has been proposed that these immune cells could decrease the immunogenicity of vaccines administered in newborns and infants. In this article, we discuss the various types of Treg cells, along with their suppressing and inhibitory mechanisms, which are used by these cells in the context of infectious and immunization processes in newborns and infants.

Sign in / Sign up

Export Citation Format

Share Document