Impaired functions of macrophage from cystic fibrosis patients: CD11b, TLR-5 decrease and sCD14, inflammatory
Karin Simonin-Le Jeune1, André Le Jeune, Stéphane Jouneau
1Université de Rennes 1, Structure Fédérative de Recherche Biosit, F-35043 Rennes, France ; Institut de Recherche Santé Environnement & Travail (IRSET), Institut National de la Santé et de la Recherche Médicale (INSERM), U1085, team 'Stress Membrane and Signaling', F-35043 Rennes, France.
Plos One
|October 8, 2013
Summary
Cystic fibrosis (CF) macrophages exhibit excessive inflammation, overproducing cytokines and showing impaired pathogen clearance due to CFTR defects. This dysfunction contributes to chronic infection and inflammation in CF patients.
Area of Science:
- Immunology
- Cell Biology
- Respiratory Medicine
Background:
- Cystic Fibrosis (CF) patients experience early microbial infections, with macrophages potentially playing a key role in disease initiation.
- Macrophage dysfunction, possibly linked to CFTR mutations, may precede chronic inflammation and infection in CF.
- Existing research often overlooks the role of macrophages, focusing more on neutrophils and epithelial cells.
Purpose of the Study:
- To investigate intrinsic macrophage defects in CF patients related to impaired Cystic Fibrosis Transmembrane conductance Regulator (CFTR) function.
- To compare inflammatory cytokine secretion, pathogen recognition, and phagocytosis in macrophages from CF patients versus healthy controls.
Main Methods:
- Studied peripheral blood monocyte-derived macrophages from stable adult CF patients and non-CF healthy subjects.
- Assessed inflammatory cytokine levels (sCD14, IL-1β, IL-6, TNF-α, IL-10) in macrophage supernatants.
- Measured cell surface marker expression (CD11b, TLR-5, mCD14, CD16, CD64, TLR-4, TLR1/TLR-2) and phagocytic activity.
Main Results:
- CF macrophages showed significantly elevated levels of sCD14 and inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-10).
- Decreased expression of CD11b and TLR-5 was observed on CF macrophages, while other markers remained unchanged.
- CF macrophages exhibited impaired phagocytosis, a defect also replicated by inhibiting CFTR in non-CF macrophages.
Conclusions:
- CF macrophages display excessive inflammation, characterized by cytokine overproduction and reduced CD11b/TLR-5 expression.
- Impaired phagocytosis and pathogen clearance by CF macrophages contribute to non-resolution of infection and exaggerated inflammation.
- These findings highlight macrophage dysfunction as a critical factor in the inflammatory cycle of cystic fibrosis.
Related Concept Videos
01:23Cystic Fibrosis: Pathogenesis
1.1K
Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
1.1K
01:25Inflammatory Bowel Disease III: Crohn's Disease
75
Crohn’s disease is a chronic, relapsing form of inflammatory bowel disease characterized by segmental, transmural inflammation that can affect any part of the gastrointestinal tract. Its pathogenesis arises from a combination of genetic susceptibility, environmental exposures, epithelial barrier dysfunction, and immune dysregulation. Together, these factors lead to an exaggerated immune response against components of the gut microbiome.Genetic and Environmental InfluencesMultiple genetic...
75
01:24Cystic Fibrosis: Management
658
Cystic fibrosis (CF) is an autosomal recessive disorder that predominantly affects individuals of Northern European descent, occurring at a rate of 1 in 3500. It is caused by a genetic mutation in a gene on chromosome 7, most commonly the ΔF508 mutation, that codes for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This results in thicker mucus secretions and obstruction pathologies in multiple organs, including the lungs and sinuses.
Sinus disease and chronic...
Sinus disease and chronic...
658
01:12Chronic Inflammation: Introduction
51
Chronic inflammation is a prolonged, dysregulated immune response that persists for weeks to years when the inciting stimulus is difficult to eradicate or when self‑antigens drive ongoing reactivity. Morphologically, it is defined by mononuclear cell infiltration, progressive tissue destruction, and concurrent attempts at healing via angiogenesis and fibrosis. Compared with acute inflammation, edema is less prominent while cellular infiltration predominates; triggers include persistent...
51
01:20Chronic Obstructive Pulmonary Disease-II: Pathophysiology
5.0K
Chronic Obstructive Pulmonary Disease (COPD) pathophysiology is intricate and multifaceted, involving a complex interplay of physiological processes. Understanding these mechanisms is crucial for effectively managing and treating COPD. Here is an in-depth look at the critical elements in the pathophysiology of COPD:
Chronic Inflammation
Chronic Inflammation
5.0K
01:24Chronic Obstructive Pulmonary Disease III: Chronic Bronchitis Features
77
Chronic bronchitis is a key phenotype of chronic obstructive pulmonary disease (COPD), characterized by airway-centered inflammation and mucus overproduction. It develops from long-term exposure to harmful particles or gases, most commonly cigarette smoke, which triggers a persistent inflammatory response.Cellular and Structural ChangesInflammation initially affects the large bronchi and later the smaller airways, with infiltration by immune cells, including neutrophils, macrophages, and...
77