Steroid-induced Deficiency of Mucosal-associated Invariant T Cells in the Chronic Obstructive Pulmonary Disease Lung. Implications for Nontypeable Haemophilus influenzae Infection
Abstract:Rationale: Mucosal-associated invariant T (MAIT) cells are a recently described abundant, proinflammatory T-cell subset with unknown roles in pulmonary immunity. Nontypeable Haemophilus influenzae (NTHi) is the leading bacterial pathogen during chronic obstructive pulmonary disease (COPD) exacerbations and is a plausible target for MAIT cells.Objectives: To investigate whether MAIT cells respond to NTHi and the effects of inhaled corticosteroids (ICS) on their frequency and function in COPD.Methods: Eleven sub… Show more
“…MAIT are a group of innate-like T lymphocytes that which are highly abundant in human blood (~1–10% [100]) and in mucosal tissues such as the intestine and lungs [101–104]. These cells are characterized by their expression of the invariant T-cell receptor (TCR) α chain, TRAV1–2 joined with TRAJ33 and a limited range of TCRβ chains, and abundant expression of CD161 and CD218 (IL18Rα) [102, 105, 106].…”
Section: Mucosal-associated Invariant T Cellsmentioning
confidence: 99%
“…The frequency of MAIT cells in normal human lungs ranges from 2 to 20% of all T cells [104, 117]. Given their abundance in blood, many studies have examined blood MAIT cells in various respiratory diseases.…”
Section: Mucosal-associated Invariant T Cellsmentioning
confidence: 99%
“…Given their abundance in blood, many studies have examined blood MAIT cells in various respiratory diseases. There were no change in MAIT cell frequency in the blood of inhaled corticosteroid (ICS)-naive COPD patients relative to healthy donors; however, their frequency was significantly reduced in ICS-treated COPD patients’ blood and bronchial biopsies [104]. The reduced MAIT cell frequency in blood was more pronounced in moderate-to-severe-COPD patients, and it was associated with elevated serum C-reactive protein levels and a reduced lung function [118].…”
Section: Mucosal-associated Invariant T Cellsmentioning
The respiratory tract is faced daily with 10,000 L of inhaled air. While the majority of air contains harmless environmental components, the pulmonary immune system also has to cope with harmful microbial or sterile threats and react rapidly to protect the host at this intimate barrier zone. The airways are endowed with a broad armamentarium of cellular and humoral host defense mechanisms, most of which belong to the innate arm of the immune system. The complex interplay between resident and infiltrating immune cells and secreted innate immune proteins shapes the outcome of host-pathogen, host-allergen, and host-particle interactions within the mucosal airway compartment. Here, we summarize and discuss recent findings on pulmonary innate immunity and highlight key pathways relevant for biomarker and therapeutic targeting strategies for acute and chronic diseases of the respiratory tract.
“…MAIT are a group of innate-like T lymphocytes that which are highly abundant in human blood (~1–10% [100]) and in mucosal tissues such as the intestine and lungs [101–104]. These cells are characterized by their expression of the invariant T-cell receptor (TCR) α chain, TRAV1–2 joined with TRAJ33 and a limited range of TCRβ chains, and abundant expression of CD161 and CD218 (IL18Rα) [102, 105, 106].…”
Section: Mucosal-associated Invariant T Cellsmentioning
confidence: 99%
“…The frequency of MAIT cells in normal human lungs ranges from 2 to 20% of all T cells [104, 117]. Given their abundance in blood, many studies have examined blood MAIT cells in various respiratory diseases.…”
Section: Mucosal-associated Invariant T Cellsmentioning
confidence: 99%
“…Given their abundance in blood, many studies have examined blood MAIT cells in various respiratory diseases. There were no change in MAIT cell frequency in the blood of inhaled corticosteroid (ICS)-naive COPD patients relative to healthy donors; however, their frequency was significantly reduced in ICS-treated COPD patients’ blood and bronchial biopsies [104]. The reduced MAIT cell frequency in blood was more pronounced in moderate-to-severe-COPD patients, and it was associated with elevated serum C-reactive protein levels and a reduced lung function [118].…”
Section: Mucosal-associated Invariant T Cellsmentioning
The respiratory tract is faced daily with 10,000 L of inhaled air. While the majority of air contains harmless environmental components, the pulmonary immune system also has to cope with harmful microbial or sterile threats and react rapidly to protect the host at this intimate barrier zone. The airways are endowed with a broad armamentarium of cellular and humoral host defense mechanisms, most of which belong to the innate arm of the immune system. The complex interplay between resident and infiltrating immune cells and secreted innate immune proteins shapes the outcome of host-pathogen, host-allergen, and host-particle interactions within the mucosal airway compartment. Here, we summarize and discuss recent findings on pulmonary innate immunity and highlight key pathways relevant for biomarker and therapeutic targeting strategies for acute and chronic diseases of the respiratory tract.
“…Intrahepatic MAIT cells have been shown to be highly activated and express CD69, HLA‐DR and CD38, and are positioned around bile ducts within hepatic portal tracts 111, 118. Furthermore, as their name suggests, they are abundant within the gut, particularly in the jejunum and colon10, 119 through their expression of gut‐homing markers α 4 β 7 and CCR9,11, 13, 118 as well as the lungs 120…”
Section: Functional Similarities Between Nk Cell and Cd8+ T‐cell Subsetsmentioning
SummaryNew data in the worlds of both innate‐like CD8+ T‐cells and natural killer (NK) cells have, in parallel, clarified some of the phenotypes of these cells and also their associated functions. While these cells are typically viewed entirely separately, the emerging innate functions of T‐cells and, similarly, the adaptive functions of NK cells suggest that many behaviours can be considered in parallel. In this review we compare the innate functions of CD8+ T‐cells (especially mucosal‐associated invariant T‐cells) and those of NK cells, and how these relate to expression of phenotypic markers, especially CD161 and CD56.
“…Although they are able to recognize a wide variety of bacteria microorganisms, bacteria that do not express riboflavin synthesis pathways do not stimulate MAIT cells(114). Hinks and colleagues demonstrated that in 11 patients who were exposed to inhaled corticosteroids, peripheral serum and bronchial biopsies contained less MAIT cells compared to healthy controls(115). In in vitro studies, non-typeable Haemophilus influenzae (NTHi) infection of macrophages obtained from healthy subjects were exposed to fluticasone or budesonide.…”
The use of culture-independent techniques has allowed us to appreciate that the upper and lower respiratory tract contain a diverse community of microbes in health and disease. Research has only recently explored the effects of the microbiome on the host immune response. The exposure of the human body to the bacterial environment is an important factor for immunological development; thus, the interaction between the microbiome and its host is critical to understanding the pathogenesis of disease. In this article, we discuss the mechanisms that determine the composition of the airway microbiome and its effects on the host immune response. With the use of ecological principles, we have learned how the lower airways constitute a unique niche subjected to frequent microbial migration (e.g., through aspiration) and constant immunological pressure. The discussion will focus on the possible inflammatory pathways that are up- and downregulated when the immune system is challenged by dysbiosis. Identification of potential markers and microbial targets to address the modulation of inflammation in early disease, when changes may have the most effect, will be critical for future therapies.
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