scholarly journals Aging-Related Impairments to M Cells in Peyer’s Patches Coincide With Disturbances to Paneth Cells

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.

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.


2013 ◽  
Vol 6 (5) ◽  
pp. 1027-1037 ◽  
Author(s):  
A Kobayashi ◽  
D S Donaldson ◽  
C Erridge ◽  
T Kanaya ◽  
I R Williams ◽  
...  

1998 ◽  
Vol 66 (8) ◽  
pp. 3758-3766 ◽  
Author(s):  
V. Behrana Jensen ◽  
John T. Harty ◽  
Bradley D. Jones

ABSTRACT Invasive enteric bacteria must pass through the intestinal epithelium in order to establish infection. It is becoming clear that a common target for intestinal mucosa penetration is the specialized epithelial cell of Peyer’s patches, the M cell. In order to gain a better understanding of how bacteria interact with M cells, we have compared the interactions of Salmonella typhimurium,Listeria monocytogenes, and Shigella flexneriwith M cells by using a murine ligated-loop model. Our results indicate that S. typhimurium possesses a highly efficient mechanism for M cell entry that targets and destroys these cells, while L. monocytogenes and S. flexneri appear to be internalized into M cells in a less disruptive fashion. Early uptake ofListeria or Shigella into M cells appeared to lead to the death of some cells, as evidenced by the appearance of holes in the intestinal epithelium. At later time points, the follicle-associated epithelium of animals infected with these bacteria displayed extensive destruction. These data indicate that enteric pathogens use different strategies to interact with M cells and initiate infection of a host.


2021 ◽  
Author(s):  
Joel Johnson George ◽  
Fabio Tadeu Arrojo Martins ◽  
Laura Martin-Diaz ◽  
Keijo Viiri

Microfold cells (M cells) are a specialized subset of epithelial intestinal cells responsible for immunosurveillance of the gastrointestinal tract. M cells are located in the Peyer's patches and are crucial for monitoring and the transcytosis of antigens, microorganisms, and pathogens via their mature receptor GP2. A mature M cell with Gp2 receptor aids in the uptake of antigens, which are passed through the single layer of epithelium and presented to underlying antigen-presenting cells and processed further down-stream with B cells, T cells, and dendritic cells. Recent studies revealed several transcription factors and ligands responsible for the development and differentiation of mature M cells however, an exhaustive list of factors remains to be elucidated. Our recent work on the epigenetic regulation of M cell development found 12 critical transcription factors that were controlled by the polycomb recessive complex 2. Musculoaponeurotic fibrosarcoma transcription factor (Maf) was identified as a gene regulated by the polycomb repressive complex (PRC2) during the development of M cells. In this paper, we explore Maf's critical role in M cell differentiation and maturation. Maf falls under the purview of RANKL signaling, is localized in the Peyer's patches of the intestine, and is expressed by M cells. Given that, complete knockout of the Maf gene leads to a lethal phenotype, organoids isolated from Maf knockout mice and treated with RANKL exhibited impaired M cell development and a significant decrease in Gp2 expression. These findings reveal that Maf is an important regulator for M cell development and differentiation.


2017 ◽  
Vol 79 (11) ◽  
pp. 1826-1835 ◽  
Author(s):  
Hideto YUASA ◽  
Youhei MANTANI ◽  
Natsumi MASUDA ◽  
Miho NISHIDA ◽  
Masaya ARAI ◽  
...  

2011 ◽  
Vol 300 (3) ◽  
pp. G442-G453 ◽  
Author(s):  
Tetsuya Hondo ◽  
Takashi Kanaya ◽  
Ikuro Takakura ◽  
Hitoshi Watanabe ◽  
Yu Takahashi ◽  
...  

Microfold (M) cells in the follicle-associated epithelium (FAE) of Peyer's patches have an important role in mucosal immune responses. A primary difficulty for investigations of bovine M cells is the lack of a specific molecular marker. To identify such a marker, we investigated the expression of several kinds of intermediate filament proteins using calf Peyer's patches. The expression patterns of cytokeratin (CK) 18 in jejunal and ileal FAE were very similar to the localization pattern of M cells recognized by scanning electron microscopy. Mirror sections revealed that jejunal CK18-positive cells had irregular and sparse microvilli, as well as pocket-like structures containing lymphocytes, typical morphological characteristic of M cells. However, CK18-negative cells had regular and dense microvilli on their surface, typical of the morphology of enterocytes. In contrast, CK20 immunoreactivity was detected in almost all villous epithelial cells and CK18-negative cells in the FAE. CK18-positive proliferating transit-amplifying cells in the crypt exchanged CK18 for CK20 above the mouth of the crypt and after moving to the villi; however, CK18-positive M cells in the crypt continued their expression of CK18 during movement to the FAE region. Terminal deoxynucleotidyl-transferase-mediated deoxyuridine-triphosphate-biotin nick-end labeling-positive apoptotic cells were specifically detected at the apical region of villi and FAE in the jejunum and ileum, and all were also stained for CK20. These data indicate that CK18 may be a molecular marker for bovine M cells in FAE and that M cells may transdifferentiate to CK20-positive enterocytes and die by apoptosis in the apex of the FAE.


1994 ◽  
Vol 180 (1) ◽  
pp. 15-23 ◽  
Author(s):  
B D Jones ◽  
N Ghori ◽  
S Falkow

Salmonella species are known to initiate infection of mammalian hosts by penetrating the intestinal epithelium of the small bowel. These bacteria preferentially interact with Peyer's patches which are collections of lymphoid follicles making up the gut-associated lymphoid tissue. We infected murine ligated intestinal loops with invasive and noninvasive Salmonella typhimurium strains for 30, 60, 120, and 180 min and examined the infected tissue by transmission electron microscopy. Within 30 min, we found that invasive S. typhimurium exclusively entered M cells found within the follicle-associated epithelium (FAE) of the Peyer's patches. Initially, interactions between invasive bacteria and enterocytes adjacent to the M cells were not found. Invasion of M cells was associated with the ability of the bacteria to invade tissue culture cells. S. typhimurium mutants, which were noninvasive for tissue culture cells, could not be found in ligated loops associated with M cells or enterocytes after incubations of 30, 60, 120, or 180 min. At 60 min, internalized invasive S. typhimurium were cytotoxic for the M cells. Destruction of an M cell formed a gap in the FAE which allowed organisms to invade enterocytes adjacent to the dead cell. Later in the infection process (120 and 180 min), the presence of bacteria beneath the FAE correlated with changes in the cytoarchitecture of the lymphoid follicle. In addition, replicating Salmonella began to enter both the apical and basolateral surfaces of enterocytes adjacent to infected M cells.


1988 ◽  
Vol 34 (10) ◽  
pp. 1142-1147 ◽  
Author(s):  
Richard I. Walker ◽  
Elsa A. Schmauder-Chock ◽  
Joe L. Parker ◽  
Donald Burr

M cells in the Peyer's patches may facilitate transport of pathogens such as Campylobacter jejuni from the intestine. We evaluated this hypothesis by using electron microscopy to examine Peyer's patches in ligated adult rabbit ileal loops inoculated with 5-mL suspensions of 109 cfu/mL of Campylobacter jejuni. Peyer's patches taken at intervals from 15 min to 2 h after inoculation of loops in anaesthetized rabbits provided evidence that Campylobacter jejuni selectively adhered to M cells as opposed to absorptive epithelial cells and was transported, apparently intact, into the M cell follicle. Although intercellular organisms were seen within the follicle, many others were phagocytosed by lymphoid cells. The proximity of the lymphatic and blood circulatory systems to the M cell follicle makes this a probable route for systemic spread of Campylobacter jejuni.


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