scholarly journals Type 2 innate immunity drives distinct neonatal immune profile conducive for heart regeneration

Theranostics ◽  
2022 ◽  
Vol 12 (3) ◽  
pp. 1161-1172
Author(s):  
Francis M. Chen ◽  
Joyce KY Tse ◽  
Leigang Jin ◽  
Chui Yiu Bamboo Chook ◽  
Fung Ping Leung ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Heart Regeneration ◽  
Immune Profile

scholarly journals The role of selected mechanisms of innate immunity in the pathogenesis of diabetes

2021 ◽  
Vol 11 (9) ◽  
pp. 544-549
Author(s):  
Paulina Trojanowska ◽  
Magdalena Chrościńska-Krawczyk ◽  
Alina Trojanowska ◽  
Ewa Tywanek ◽  
Jakub Wronecki ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Metabolic Diseases ◽  
Inflammatory Diseases ◽  
The Body ◽  
Low Grade ◽  
Intracellular Space ◽  
Cytoplasmic Proteins

Understanding the important role of the non-specific immune response in protecting the body against the development of numerous diseases has become partially possible after the discovery of several classes of pattern recognition receptors (PRR), such as Toll-like or NOD-like receptors. A group of cytoplasmic proteins called the inflammasome, which detect PAMP and DAMP through the PRR receptors, is able to activate pro-inflammatory cytokines and trigger an acute inflammatory reaction both in the extracellular and intracellular space. Low-grade systemic and local inflammation contributes to the development and progression of various conditions, including autoimmune and metabolic diseases, such as diabetes, metabolic syndrome and atherosclerosis, which until recently were not even considered inflammatory diseases. This review will discuss the role of innate immunity in the development of type 1 and type 2 diabetes, focusing on the role of specific innate immunity receptors and insulin resistance involved in these diseases pathogenesis.

scholarly journals Mechanism of innate immune reprogramming by a fungal meningitis pathogen

2021 ◽  
Author(s):  
Eric V. Dang ◽  
Susan Lei ◽  
Atanas Radkov ◽  
Hiten Madhani
Keyword(s):  
Innate Immunity ◽  
Fungal Pathogens ◽  
Forward Genetics ◽  
Alternative Activation ◽  
Cytokine Signaling ◽  
Alternatively Activated Macrophages ◽  
Fungal Meningitis

How deadly fungal pathogens overcome mammalian innate immunity is largely unknown. Cryptococcus neoformans, the most common cause of fungal meningitis, induces a pathogenic type 2 response characterized by pulmonary eosinophilia and alternatively activated macrophages. Using forward genetics, we identified a fungal secreted protein, Cpl1, necessary and sufficient to enhance alternative activation of primary macrophages in vitro. Cpl1-enhanced polarization requires Toll-like receptor 4, a known mediator of allergen-induced type 2 responses. Cpl1 is essential for virulence, drives polarization of interstitial macrophages in vivo, and requires type 2 cytokine signaling for its impact on infectivity. C. neoformans selectively associates with polarized interstitial macrophages during infection, supporting a direct host-pathogen interaction. This work identifies a secreted effector produced by a human fungal pathogen that reprograms innate immunity to enable tissue infection.

scholarly journals Biofilm-Induced Type 2 Innate Immunity in a Cystic Fibrosis Model of Pseudomonas aeruginosa

2017 ◽  
Vol 7 ◽  
Author(s):  
Kenny Bielen ◽  
Bart ‘S Jongers ◽  
Jan Boddaert ◽  
Tom K. Raju ◽  
Christine Lammens ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Innate Immunity

Innate immunity defects in Hermansky-Pudlak type 2 syndrome

Blood ◽  
2006 ◽  
Vol 107 (12) ◽  
pp. 4857-4864 ◽  
Author(s):  
S. Fontana
Keyword(s):  
Innate Immunity

scholarly journals Activation of bone marrow adaptive immunity in type 2 diabetes: rescue by co-stimulation modulator Abatacept

2020 ◽  
Author(s):  
Marianna Santopaolo ◽  
Niall Sullivan ◽  
Anita C. Thomas ◽  
Valeria Alvino ◽  
Lindsay Nicholson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Insulin Sensitivity ◽  
Adaptive Immunity ◽  
Low Grade ◽  
Immune Profile ◽  
Adaptive Immune

AbstractHypothesisType 2 diabetes (T2D) is characterized by low-grade inflammation. Here, we investigated the state of adaptive immunity in bone marrow (BM) of patients and mice with T2D. We also tested if inhibition T cell co-stimulation by Abatacept could rescue the immune profile of T2D mice.MethodsFlow-cytometry and cytokine analyses were performed on BM samples from patients with or without T2D. Moreover, we studied the immune profile of db/db and control wt/db mice. A cohort of db/db mice was randomized to receive Abatacept or vehicle for 4 weeks, with endpoints being immune cell profile and indexes of insulin sensitivity and heart performance.ResultsT2D patients showed increased frequencies of BM CD4+ (2.8-fold, p=0.001) and CD8+ T cells (1.8-fold, p=0.01), with upregulation of the activation marker CD69 and homing receptor CCR7 in CD4+ (1.64-fold, p=0.003 and 2.27-fold, p=0.01, respectively) and CD8+ fractions (1.79-fold, p=0.05 and 1.69-fold, p=0.02, respectively). CCL19 (CCR7 receptor ligand) and CXCL10/11 (CXCR3 receptor ligands), implicated in T cell migration and activation, were the most differentially modulated chemokines. Studies in mice confirmed the activation of adaptive immunity in T2D. Abatacept reduced the activation of T cells and levels of pro-inflammatory chemokines and cytokines. Additionally, Abatacept improved indexes of cardiac systolic function, but not insulin sensitivity.ConclusionsThese novel findings support the concept of BM adaptive immune activation in T2D. Modulation of T cell co-stimulation could represent an attractive and immediately available modality to dampen inappropriate activation of adaptive immune response and protect from target organ damage.

The chemerin-CMKLR1 axis limits thermogenesis by controlling a beige adipocyte/IL-33/type 2 innate immunity circuit

2021 ◽  
Vol 6 (61) ◽  
pp. eabg9698
Author(s):  
Yuli Lin ◽  
Liuling Xiao ◽  
Qian Cai ◽  
Cuisong Zhu ◽  
Shufen Li ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Metabolic Disorders ◽  
Innate Immune ◽  
Negative Regulator ◽  
Innate Immune Responses ◽  
Cold Stimulation ◽  
Beige Adipocytes ◽  
Beige Fat

IL-33–associated type 2 innate immunity has been shown to support beige fat formation and thermogenesis in subcutaneous inguinal white adipose tissue (iWAT), but little is known about how it is regulated in iWAT. Chemerin, as a newly identified adipokine, is clinically associated with obesity and metabolic disorders. We here show that cold exposure specifically reduces chemerin and its receptor chemerin chemokine-like receptor 1 (CMKLR1) expression in iWAT. Lack of chemerin or adipocytic CMKLR1 enhances cold-induced thermogenic beige fat via potentiating type 2 innate immune responses. Mechanistically, we identify adipocytes, particularly beige adipocytes, as the main source for cold-induced IL-33, which is restricted by the chemerin-CMKLR1 axis via dampening cAMP-PKA signaling, thereby interrupting a feed-forward circuit between beige adipocytes and type 2 innate immunity that is required for cold-induced beige fat and thermogenesis. Moreover, specific deletion of adipocytic IL-33 inhibits cold-induced beige fat and type 2 innate immune responses. Last, genetic blockade of adipocytic CMKLR1 protects against diet-induced obesity and enhances the metabolic benefits of cold stimulation in preestablished obese mice. Thus, our study identifies the chemerin-CMKLR1 axis as a physiological negative regulator of thermogenic beige fat via interrupting adipose-immune communication and suggests targeting adipose CMKLR1 as a potential therapeutic strategy for obesity-related metabolic disorders.

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