scholarly journals The MAIT conundrum – how human MAIT cells distinguish bacterial colonization from infection in mucosal barrier tissues

2017 ◽  
Vol 192 ◽  
pp. 7-11 ◽  
Author(s):  
Julia D. Berkson ◽  
Martin Prlic
PEDIATRICS ◽  
1985 ◽  
Vol 75 (1) ◽  
pp. 167-171
Author(s):  
W. Allan Walker

An important adaptation of the gastrointestinal tract to the extrauterine environment is its development of a mucosal barrier against the penetration of proteins and protein fragments. To combat the potential danger of invasion across the mucosal barrier the newborn infant must develop within the lumen and on the luminal mucosal surface an elaborate system of defense mechanisms which act to control and maintain the epithelium as an impermeable barrier to the uptake of macromolecular antigens. As a result of a delay in the maturation of the mucosal barrier, newborn infants are particularly vulnerable to pathologic penetration by harmful intraluminal substances. The consequences of altered defense are susceptibility to infection and the potential for hypersensitivity reactions and the formation of immune complexes. With these reactions comes the potential for developing life-threatening diseases such as necrotizing enterocolitis, sepsis, and hepatitis. Fortunately, "nature" has provided a means for passively protectecting the "vulnerable" newborn against the dangers of a deficient intestinal defense system, namely human milk. It is now increasingly apparent that human milk contains not only antibodies and viable leukocytes but many other substances that can interfere with bacterial colonization and prevent antigen penetration.


2003 ◽  
Vol 89 (5) ◽  
pp. 597-606 ◽  
Author(s):  
Brigitta Kleessen ◽  
Ludger Hartmann ◽  
Michael Blaut

The effects of fructans in the diet on the mucosal morphometry (height of villi, depth of the crypts, number of goblet cells), the thickness of the epithelial mucus layer and the histochemical composition of intestinal mucosubstances in the distal jejunum and the distal colon were investigated by comparing germ-free (GF) rats, rats harbouringBacteroides vulgatusandBifidobacterium longum(diassociated (DA) rats), and rats with a human faecal flora (HFA). The rats were fed either a commercial standard diet (ST) or ST + (50 g oligofructose (OF)–long-chain inulin (lcIN))/kg. Changes in total bacteria, bifidobacteria andBacteroides–Prevotellain response to feeding these diets were investigated by fluorescentin situhybridization with 16S rRNA-targeted probes both in intestinal contents (lumen bacteria) and tissue sections (mucosa-associated bacteria). The OF–lcIN-containing diet resulted in higher villi and deeper crypts in bacteria-associated, but not in GF rats. In DA and HFA rats, the colonic epithelial mucus layer was thicker and the numbers of the goblet cells were greater than in GF rats. These effects were enhanced by the OF–lcIN-containing diet. In both dietary groups, bacterial colonization of GF rats caused an increase in neutral mucins in the distal jejunum and colon. Bacteria-associated rats had more acidic mucins in the colon than GF rats, and the OF–lcIN-containing diet stimulated sulfomucins as the predominant type of acidic mucins, while sialomucins dominated in the ST-fed groups. The number of mucosa-associated bifidobacteria detected in the colon of DA and HFA rats was greater with OF–lcIN than ST (4·9 and 5·4v. 3·5 and 4·0 log10/mm2mucosal surface respectively), whereas the number of luminal bifidobacteria was only affected by fructans in DA rats.Bacteroidesdid not differ between the groups. The stabilisation of the gut mucosal barrier, either by changes in the mucosal architecture itself, in released mucins or by stimulation of mucosal bifidobacteria with fructans, could become an important topic in the treatment and prophylaxis of gastrointestinal disorders and health maintenance.


2021 ◽  
Author(s):  
Mallory Paynich Murray ◽  
Catherine M. Crosby ◽  
Paola Marcovecchio ◽  
Nadine Hartmann ◽  
Shilpi Chandra ◽  
...  

Innate-like T cells, including invariant natural killer T (iNKT) cells, mucosal-associated invariant T (MAIT) cells and γδ T cells, are present in various barrier tissues, including the lung. They carry out protective responses during infections, but the mechanisms for protection are not completely understood. Here, we investigated their roles during pulmonary infection with Streptococcus pneumoniae. Following infection, innate-like T cells rapidly increased in lung tissue, in part through recruitment, but TCR activation and cytokine production occurred mostly in IL-17-producing NKT17 and γδ T cells. NKT17 cells were preferentially located outside the vasculature prior to infection, as were CD103+ dendritic cells (cDC1), which were important both for antigen presentation to NKT17 cells and γδ T cell activation. Whereas IL-17A-producing γδ T cells also were numerous, GM-CSF was exclusive to NKT17 cells and contributed to iNKT cell-mediated protection. These studies demonstrate how particular cellular interactions and responses of functional subsets of innate-like T cells contribute to protection from pathogenic lung infection.


2021 ◽  
Vol 10 (10) ◽  
pp. e489101019166 ◽  
Author(s):  
Luisa Ferreira da Cruz ◽  
Israel Lucas Antunes Souza ◽  
Larissa Dias de Souza ◽  
Marcelo Gonzaga de Freitas Araújo ◽  
Paulo Afonso Granjeiro

The gastrointestinal tract houses the largest and most complex community of microorganisms, and this bacterial colonization of the human intestine by environmental microbes begins immediately after the birth. The intestinal microbiota has several important and unique functions, including metabolic functions such as the biotransformation of drugs and the digestion of dietary compounds; a mucosal barrier function by inhibiting the invasion of pathogens and an immunomodulatory function. On the other hand, some commensal bacteria can be pathogenic, causing infections if the natural host is compromised and, in predisposed hosts, the intestinal microbiota can be involved in nosocomial infection. The translocation of bacteria through the intestinal wall is considered one of the main causes of nosocomial infections. The aim of this review is to provide a comprehensive view of the human gut microbiota, its main functions, its role in health and disease, addressing the correlation between intestinal microbial composition and nosocomial infections.


2020 ◽  
Vol 11 ◽  
Author(s):  
Ali Amini ◽  
Declan Pang ◽  
Carl-Philipp Hackstein ◽  
Paul Klenerman

Mucosal-associated invariant T (MAIT) cells are innate-like T cells present at considerable frequencies in human blood and barrier tissues, armed with an expanding array of effector functions in response to homeostatic perturbations. Analogous to other barrier immune cells, their phenotype and function is driven by crosstalk with host and dynamic environmental factors, most pertinently the microbiome. Given their distribution, they must function in diverse extracellular milieus. Tissue-specific and adapted functions of barrier immune cells are shaped by transcriptional programs and regulated through a blend of local cellular, inflammatory, physiological, and metabolic mediators unique to each microenvironment. This review compares the phenotype and function of MAIT cells with other barrier immune cells, highlighting potential areas for future exploration. Appreciation of MAIT cell biology within tissues is crucial to understanding their niche in health and disease.


Children ◽  
2021 ◽  
Vol 8 (5) ◽  
pp. 413
Author(s):  
Gustavo Nino ◽  
Carlos E. Rodriguez-Martinez ◽  
Maria J. Gutierrez

Over the past two decades, several studies have positioned early-life microbial exposure as a key factor for protection or susceptibility to respiratory diseases. Birth cohorts have identified a strong link between neonatal bacterial colonization of the nasal airway and gut with the risk for respiratory infections and childhood asthma. Translational studies have provided companion mechanistic insights on how viral and bacterial exposures in early life affect immune development at the respiratory mucosal barrier. In this review, we summarize and discuss our current understanding of how early microbial–immune interactions occur during infancy, with a particular focus on the emergent paradigm of “innate immune training”. Future human-based studies including newborns and infants are needed to inform the timing and key pathways implicated in the development, maturation, and innate training of the airway immune response, and how early microbiota and virus exposures modulate these processes in the respiratory system during health and disease.


2002 ◽  
Vol 57 (5) ◽  
pp. 243-248 ◽  
Author(s):  
Alexander Roberto Precioso ◽  
Renata Suman Mascaretti Proença

Necrotizing enterocolitis is the most frequently occurring gastrointestinal disorder in premature neonates. Animal models of necrotizing enterocolitis and prenatal administration of cortisone have demonstrated that cortisone may accelerate maturation of the mucosal barrier, therefore reducing the incidence of this gastrointestinal disorder. The authors present a review of the literature of the most important risk factors associated with necrotizing enterocolitis, such as inflammatory gastrointestinal mediators, enteral feeding and bacterial colonization, and immaturity of the gastrointestinal barrier, and we emphasize the necessity for additional studies to explore the prenatal administration of cortisone as a preventive strategy for necrotizing enterocolitis.


2009 ◽  
Vol 77 (12) ◽  
pp. 5206-5215 ◽  
Author(s):  
Gregory M. Glenn ◽  
David H. Francis ◽  
E. Michael Danielsen

ABSTRACT Recent studies have confirmed older observations that the enterotoxins enhance enteric bacterial colonization and pathogenicity. How and why this happens remains unknown at this time. It appears that toxins such as the heat-labile enterotoxin (LT) from Escherichia coli can help overcome the innate mucosal barrier as a key step in enteric pathogen survival. We review key observations relevant to the roles of LT and cholera toxin in protective immunity and the effects of these toxins on innate mucosal defenses. We suggest either that toxin-mediated fluid secretion mechanically disrupts the mucus layer or that toxins interfere with innate mucosal defenses by other means. Such a breach gives pathogens access to the enterocyte, leading to binding and pathogenicity by enterotoxigenic E. coli (ETEC) and other organisms. Given the common exposure to LT+ ETEC by humans visiting or residing in regions of endemicity, barrier disruption should frequently render the gut vulnerable to ETEC and other enteric infections. Conversely, toxin immunity would be expected to block this process by protecting the innate mucosal barrier. Years ago, Peltola et al. (Lancet 338:1285-1289, 1991) observed unexpectedly broad protective effects against LT+ ETEC and mixed infections when using a toxin-based enteric vaccine. If toxins truly exert barrier-disruptive effects as a key step in pathogenesis, then a return to classic toxin-based vaccine strategies for enteric disease is warranted and can be expected to have unexpectedly broad protective effects.


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