scholarly journals The functional maturation of M cells is dramatically reduced in the Peyer’s patches of aged mice

2013 ◽  
Vol 6 (5) ◽  
pp. 1027-1037 ◽  
Author(s):  
A Kobayashi ◽  
D S Donaldson ◽  
C Erridge ◽  
T Kanaya ◽  
I R Williams ◽  
...  
2020 ◽  
Author(s):  
David S. Donaldson ◽  
Jolinda Pollock ◽  
Prerna Vohra ◽  
Mark P. Stevens ◽  
Neil A. Mabbott

SUMMARYAgeing has a profound effect on the immune system, termed immunosenescence, resulting in increased incidence and severity of infections and decreased efficacy of vaccinations. We previously showed that immunosurveillance in the intestine, achieved primarily through antigen sampling M cells in the follicle associated epithelium (FAE) of Peyer’s patches, was compromised during ageing due to a decline in M cell functional maturation. The intestinal microbiota also changes significantly with age, but whether this affects M cell maturation was not known. We show that housing of aged mice on used bedding from young mice, or treatment with bacterial flagellin, were each sufficient to enhance the functional maturation of M cells in Peyer’s patches. An understanding of the mechanisms underlying the influence of the intestinal microbiota on M cells has the potential to lead to new methods to enhance the efficacy of oral vaccination in aged individuals.


2021 ◽  
Vol 12 ◽  
Author(s):  
David S. Donaldson ◽  
Barbara B. Shih ◽  
Neil A. Mabbott

The decline in mucosal immunity during aging increases susceptibility, morbidity and mortality to infections acquired via the gastrointestinal and respiratory tracts in the elderly. We previously showed that this immunosenescence includes a reduction in the functional maturation of M cells in the follicle-associated epithelia (FAE) covering the Peyer’s patches, diminishing the ability to sample of antigens and pathogens from the gut lumen. Here, co-expression analysis of mRNA-seq data sets revealed a general down-regulation of most FAE- and M cell-related genes in Peyer’s patches from aged mice, including key transcription factors known to be essential for M cell differentiation. Conversely, expression of ACE2, the cellular receptor for SARS-Cov-2 virus, was increased in the aged FAE. This raises the possibility that the susceptibility of aged Peyer’s patches to infection with the SARS-Cov-2 virus is increased. Expression of key Paneth cell-related genes was also reduced in the ileum of aged mice, consistent with the adverse effects of aging on their function. However, the increased expression of these genes in the villous epithelium of aged mice suggested a disturbed distribution of Paneth cells in the aged intestine. Aging effects on Paneth cells negatively impact on the regenerative ability of the gut epithelium and could indirectly impede M cell differentiation. Thus, restoring Paneth cell function may represent a novel means to improve M cell differentiation in the aging intestine and increase mucosal vaccination efficacy in the elderly.


2010 ◽  
Vol 341 (3) ◽  
pp. 417-427 ◽  
Author(s):  
Feyzullah Beyaz ◽  
Emel Ergün ◽  
Alev G. Bayraktaroğlu ◽  
Levent Ergün

2010 ◽  
Vol 78 (8) ◽  
pp. 3570-3577 ◽  
Author(s):  
Luiz E. Bermudez ◽  
Mary Petrofsky ◽  
Sandra Sommer ◽  
Raúl G. Barletta

ABSTRACT Mycobacterium avium subsp. paratuberculosis, the agent of Johne's disease, infects ruminant hosts by translocation through the intestinal mucosa. A number of studies have suggested that M. avium subsp. paratuberculosis interacts with M cells in the Peyer's patches of the small intestine. The invasion of the intestinal mucosa by M. avium subsp. paratuberculosis and Mycobacterium avium subsp. hominissuis, a pathogen known to interact with intestinal cells, was compared. M. avium subsp. paratuberculosis was capable of invading the mucosa, but it was significantly less efficient at dissemination than M. avium subsp. hominissuis. B-cell knockout (KO) mice, which lack Peyer's patches, were used to demonstrate that M. avium subsp. paratuberculosis enters the intestinal mucosa through enterocytes in the absence of M cells. In addition, the results indicated that M. avium subsp. paratuberculosis had equal abilities to cross the mucosa in both Peyer's patch and non-Peyer's patch segments of normal mice. M. avium subsp. paratuberculosis was also shown to interact with epithelial cells by an α5β1 integrin-independent pathway. Upon translocation, dendritic cells ingest M. avium subsp. paratuberculosis, but this process does not lead to efficient dissemination of the infection. In summary, M. avium subsp. paratuberculosis interacts with the intestinal mucosa by crossing both Peyer's patches and non-Peyer's patch areas but does not translocate or disseminate efficiently.


2004 ◽  
Vol 78 (2) ◽  
pp. 947-957 ◽  
Author(s):  
Amy B. Hutchings ◽  
Anna Helander ◽  
Katherine J. Silvey ◽  
Kartik Chandran ◽  
William T. Lucas ◽  
...  

ABSTRACT Reovirus type 1 Lang (T1L) adheres to M cells in the follicle-associated epithelium of mouse intestine and exploits the transport activity of M cells to enter and infect the Peyer's patch mucosa. Adult mice that have previously cleared a reovirus T1L infection have virus-specific immunoglobulin G (IgG) in serum and IgA in secretions and are protected against reinfection. Our aim in this study was to determine whether secretory IgA is sufficient for protection of Peyer's patches against oral reovirus challenge and, if so, against which reovirus antigen(s) the IgA may be directed. Monoclonal antibodies (MAbs) of the IgA isotype, directed against the σ1 protein of reovirus T1L, the viral adhesin, were produced and tested along with other, existing IgA and IgG MAbs against reovirus T1L outer capsid proteins. Anti-σ1 IgA and IgG MAbs neutralized reovirus T1L in L cell plaque reduction assays and inhibited T1L adherence to L cells and Caco-2BBe intestinal epithelial cells in vitro, but MAbs against other proteins did not. Passive oral administration of anti-σ1 IgA and IgG MAbs prevented Peyer's patch infection in adult mice, but other MAbs did not. When anti-σ1 IgA and IgG MAbs were produced in mice from hybridoma backpack tumors, however, the IgA prevented Peyer's patch infection, but the IgG did not. The results provide evidence that neutralizing IgA antibodies specific for the σ1 protein are protective in vitro and in vivo and that the presence of these antibodies in intestinal secretions is sufficient for protection against entry of reovirus T1L into Peyer's patches.


2019 ◽  
Vol 18 (4) ◽  
pp. 67-75
Author(s):  
V. H. Hryn ◽  
Yu. P. Kostylenko

Over the past two decades, there have been many publications dealing with the further development of an urgent issue on the immune system of the mucous membranes of the digestive tract, called mucoseassociated lymphoid tissue (MALT), which includes spheres of innate (non-specific) and adaptive (specific) immunity. Most structured formations and indicators of adaptive immunity in the intestinal mucosa are lymphoepithelial formation (Peyer's patches). The data on the formation of the peripheral part of the immune system are carried through the epithelium, mechanisms of interaction between pathogenic intestinal microflora and immunocompetent cells, thereby initiating the development of immune responses in the mucous membranes. A concept has long been established in the literature, according to which a leading role in mediating these reactions belongs to a special type of enterocytes, called M-cells. Before the concept of the initial role of these cells in the development of immune responses in the mucous membranes of the intestinal tract they were known as caveolated cells. The purpose of this study was to determine the shape and topological relations of M-cells with other types of enterocytes, and also with lymphoid elements Peyer's patches of the small intestine. 30 mature albino male rats weighted 200,0±20,0 g were involved into the study. After vivisection, which was carried out by an overdose of thiopental anesthesia (75 mg / kg of animal body weight intramuscularly in the upper third of the thigh of the hind paw) [1] in compliance with the requirements for dissection of the abdominal cavity, the entire complex of the gastrointestinal tract was removed, which was preserved in 10 % formalin solution. Subsequently, short sections of the small intestine, containing Peyer’s patches, were selectively excised. Finding the latter was not difficult due to their clear visualization on the external (nonmesenteric) surface of the small intestine in the form of whitish spots. The specimens, after washing from formalin and dehydration in alcohol of increasing concentration, were embedded into paraffin blocks, from which serial sections of 4 µm thick (Microm HM 325) were obtained with subsequent staining with hematoxylin-eosin and Van Gieson. Their study and documentation was carried out using the “Konus” light microscope equipped with the Sigeta DCM-900 9.0MP digital microphoto attachment and the Biorex 3 program (serial number 5604) adapted for these studies. In the study of many series of paraffin sections stained with hematoxylin-eosin, it was found that while maintaining the general shape of the structure, lymphoid nodules are susceptible to plastic variability, which depends on situationally changing factors of antigenic effect, i.e., functional polymorphism is characteristic of them. This is especially true of their lymphoidassociated epithelium, which appears in a rather diverse form, which depends not only on the section angle, but also, probably, on its reactive state. Thus, in some cases it is a relatively even monolayer of intestinal epithelium, consisting mainly of absorbing enterocytes, among which the most distinct are goblet cells. At the same time, it draws attention to itself that in the apical sections of some of them there are clear signs of rupture of the plasmolemma and the presence in the cytoplasm of basophilic granular fibrous material of an unknown nature. Along with this picture, other histological sections of large lymphoid nodules of Peyer's patches of the small intestine demonstrate a different configurational character of lymphoid-associated epithelium, in which the cluster principle of cell distribution in the form of limited portioned sets is clearly noted. While maintaining the general structural shape, Peyer's patches were found to be subjected to plastic variability, which depends on situationally changing factors of antigenic exposure, i.e., functional polymorphism is characteristic of them. This is especially true of their lymphoid-associated epithelium. Identification of M-cells using only traditional histological methods in practice is complicated. And yet, in the process of a focused study of serial paraffin sections, it was possible to detect some morphological signs indicating their location.


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