scholarly journals Identification of scavenger receptor B1 as the airway microfold cell receptor for Mycobacterium tuberculosis

2019 ◽  
Author(s):  
Haaris S. Khan ◽  
Vidhya R. Nair ◽  
Cody R. Ruhl ◽  
Samuel Alvarez-Arguedas ◽  
Jorge L. Galvan Resendiz ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Scavenger Receptor ◽  
Cell Receptor ◽  
The Body ◽  
M Cells ◽  
M Cell ◽  
Type Vii Secretion ◽  
Multiple Routes ◽  
Mechanistic Basis ◽  
Microfold Cells

AbstractMycobacterium tuberculosis (Mtb) can enter the body through multiple routes, including via specialized transcytotic cells called microfold cells (M cell). However, the mechanistic basis for M cell entry remains undefined. Here, we show that M cell transcytosis depends on the Mtb Type VII secretion machine and its major virulence factor EsxA. We identify scavenger receptor B1 (SR-B1) as an EsxA receptor on airway M cells. SR-B1 is required for Mtb binding to and translocation across M cells in mouse and human tissue. Together, our data demonstrate a previously undescribed role for Mtb EsxA in mucosal invasion and identify SR-B1 as the airway M cell receptor for Mtb.

scholarly journals Identification of scavenger receptor B1 as the airway microfold cell receptor for Mycobacterium tuberculosis

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Haaris S Khan ◽  
Vidhya R Nair ◽  
Cody R Ruhl ◽  
Samuel Alvarez-Arguedas ◽  
Jorge L Galvan Rendiz ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Scavenger Receptor ◽  
Cell Receptor ◽  
The Body ◽  
M Cells ◽  
M Cell ◽  
Type Vii Secretion ◽  
Multiple Routes ◽  
Mechanistic Basis ◽  
Microfold Cells

Mycobacterium tuberculosis (Mtb) can enter the body through multiple routes, including via specialized transcytotic cells called microfold cells (M cell). However, the mechanistic basis for M cell entry remains undefined. Here, we show that M cell transcytosis depends on the Mtb Type VII secretion machine and its major virulence factor EsxA. We identify scavenger receptor B1 (SR-B1) as an EsxA receptor on airway M cells. SR-B1 is required for Mtb binding to and translocation across M cells in mouse and human tissue. Together, our data demonstrate a previously undescribed role for Mtb EsxA in mucosal invasion and identify SR-B1 as the airway M cell receptor for Mtb.

scholarly journals Atoh8 is a regulator of intestinal microfold cell (M cell) differentiation

2021 ◽  
Author(s):  
Joel Johnson George ◽  
Laura Martin Diaz ◽  
Markus Ojanen ◽  
Keijo Viiri
Keyword(s):  
Cell Differentiation ◽  
Mucosal Immunity ◽  
M Cells ◽  
M Cell ◽  
Polycomb Repressive Complex 2 ◽  
Salmonella Infections ◽  
Epigenetic Regulator ◽  
Development And Differentiation ◽  
Host Mouse ◽  
Microfold Cells

Intestinal microfold cells (M cells) are a dynamic lineage of epithelial cells that initiate mucosal immunity in the intestine. They are responsible for the uptake and transcytosis of microorganisms, pathogens and other antigens in the gastrointestinal tract. A mature M cell expresses a receptor Gp2 which binds to pathogens and aids in the uptake. Due to the rarity of these cells in the intestine, its development and differentiation remains yet to be fully understood. We recently demonstrated that polycomb repressive complex 2 (PRC2) is an epigenetic regulator of M cell development and 12 novel transcription factors including Atoh8 were revealed to be regulated by the PRC2. Here, we show that Atoh8 acts as a regulator of M cell differentiation; absence of Atoh8 led to a significant increase in the number of Gp2+ mature M cells and other M cell associated markers. Atoh8 null mice showed an increase in transcytosis capacity of luminal antigens. Increase in M cell population has been previously reported to be detrimental to mucosal immunity because some pathogens like orally acquired prions have been able to exploit the transcytosis capacity of M cells to infect the host; mouse with increased population of M cells are also susceptible to Salmonella infections. Our study here demonstrates that the population density of intestinal M-cell in the Peyer's patch is regulated by the PRC2 regulated Atoh8.

scholarly journals PRC2 Regulated Atoh8 Is a Regulator of Intestinal Microfold Cell (M Cell) Differentiation

2021 ◽  
Vol 22 (17) ◽  
pp. 9355
Author(s):  
Joel Johnson George ◽  
Laura Martin-Diaz ◽  
Markus J. T. Ojanen ◽  
Rosa Gasa ◽  
Marko Pesu ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Mucosal Immunity ◽  
M Cells ◽  
M Cell ◽  
Polycomb Repressive Complex 2 ◽  
Salmonella Infections ◽  
Epigenetic Regulator ◽  
Development And Differentiation ◽  
Microfold Cells

Intestinal microfold cells (M cells) are a dynamic lineage of epithelial cells that initiate mucosal immunity in the intestine. They are responsible for the uptake and transcytosis of microorganisms, pathogens, and other antigens in the gastrointestinal tract. A mature M cell expresses a receptor Gp2 which binds to pathogens and aids in the uptake. Due to the rarity of these cells in the intestine, their development and differentiation remain yet to be fully understood. We recently demonstrated that polycomb repressive complex 2 (PRC2) is an epigenetic regulator of M cell development, and 12 novel transcription factors including Atoh8 were revealed to be regulated by the PRC2. Here, we show that Atoh8 acts as a regulator of M cell differentiation; the absence of Atoh8 led to a significant increase in the number of Gp2+ mature M cells and other M cell-associated markers such as Spi-B and Sox8. In vitro organoid analysis of RankL treated organoid showed an increase of mature marker GP2 expression and other M cell-associated markers. Atoh8 null mice showed an increase in transcytosis capacity of luminal antigens. An increase in M cell population has been previously reported to be detrimental to mucosal immunity because some pathogens like orally acquired prions have been able to exploit the transcytosis capacity of M cells to infect the host; mice with an increased population of M cells are also susceptible to Salmonella infections. Our study here demonstrates that PRC2 regulated Atoh8 is one of the factors that regulate the population density of intestinal M cell in the Peyer’s patch.

Spinal Circuit for Escape in Goldfish and Zebrafish

2017 ◽  
pp. 517-520
Author(s):  
Joseph R. Fetcho
Keyword(s):  
Spinal Cord ◽  
Escape Behavior ◽  
The Body ◽  
M Cells ◽  
M Cell ◽  
Potential Threat ◽  
Reticulospinal Neurons ◽  
Bilateral Pair ◽  
The Brain ◽  
Spinal Circuit

Escape or startle responses are vital to organisms. In fishes, escape behavior is a rapid bend of the body and tail away from a potential threat that occurs within milliseconds after a stimulus. When properly executed, it is a fast, powerful body bend to only one side that takes precedence over any other movements. The behavior is initiated by the firing of one of a bilateral pair of hindbrain reticulospinal neurons (RSNs) called Mauthner cells (M-cells). The output of each cell occurs via an axon that crosses in the brain and extends the length of the spinal cord on the opposite side of the body. The circuit of the M-cell in spinal cord is based upon studies of goldfish and zebrafish. This circuit, repeated along the spinal cord, has several features that are well matched to the behavioral demands of escape movements.

scholarly journals Role of M Cells in Human Mucosal Immunity to Mycobacterium tuberculosis

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S48-S48
Author(s):  
Vidhya Nair ◽  
Haaris Khan ◽  
Ron Mitchell ◽  
Michael U Shiloh
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Virulence Factor ◽  
Mucosal Immunity ◽  
Cell Biology ◽  
Infection Model ◽  
M Cells ◽  
Dependent Manner ◽  
M Cell ◽  
Wide Range

Abstract Background Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is a bacterial pathogen that infects roughly one-third of the worldÕs population and causes 1–2 million deaths per year. The current paradigm is that phagocytosis of Mtb by patrolling alveolar macrophages initiates Mtb infection. While this model can account for pulmonary TB, it does not adequately explain the occurrence of extrapulmonary forms of TB that manifest in the absence of obvious lung involvement, such as tuberculous cervical lymphadenitis, also known as scrofula. We hypothesized that specialized epithelial cells called microfold cells (M cells) may be an alternate portal of entry for Mtb. Previously we demonstrated that Mtb is able to transcytose across an epithelial barrier in an M cell dependent manner and that M cell mediated transcytosis is vital for Mtb pathogenesis in a mouse model of tuberculosis. Methods We used an in vitro M-cell mediated translocation assay and a Mtb mutant lacking a key virulence factor, ESAT6. We used biochemistry and genetics to identify a novel receptor for ESAT6. We also developed a novel explanted human adenoid Mtb infection model to study mucosal immunity. Results We now demonstrate that the Mtb virulence factor ESAT6 is necessary and sufficient to mediate binding and transcytosis by M cells in vitro and in vivo, and that uptake of Mtb by M cells requires a unique cell surface ESAT6 receptor. We developed a novel explanted human adenoid model of M cell biology and demonstrate rapid Mtb transcytosis by primary human tissue within 60–120 minutes. Using flow cytometry we find that Mtb is first ingested by M cells and then after transcytosis, by tissue resident antigen-presenting cells. Explanted adenoids from 10 independent donors display a wide range of Mtb uptake. Conclusion We conclude that Mtb ESAT6 is necessary for Mtb uptake by M-cells and that binding and transcytosis require a host receptor. Because explanted adenoids display a wide range of Mtb uptake, M cell mediated transcytosis may confer differential susceptibility to scrofula and disseminated disease. These findings are significant as M cells could potentially serve as the basis for novel therapeutic targets against primary Mtb infection. Disclosures All authors: No reported disclosures.

scholarly journals Author response: Identification of scavenger receptor B1 as the airway microfold cell receptor for Mycobacterium tuberculosis

2020 ◽  
Author(s):  
Haaris S Khan ◽  
Vidhya R Nair ◽  
Cody R Ruhl ◽  
Samuel Alvarez-Arguedas ◽  
Jorge L Galvan Rendiz ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Scavenger Receptor ◽  
Cell Receptor ◽  
Author Response

scholarly journals Role of Structural and Non-Structural Proteins and Therapeutic Targets of SARS-CoV-2 for COVID-19

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 821
Author(s):  
Rohitash Yadav ◽  
Jitendra Kumar Chaudhary ◽  
Neeraj Jain ◽  
Pankaj Kumar Chaudhary ◽  
Supriya Khanra ◽  
...  
Keyword(s):  
Host Cell ◽  
Protein S ◽  
Structural Similarity ◽  
Cell Receptor ◽  
Molecular Assembly ◽  
The Body ◽  
Spike Protein ◽  
Structural Proteins ◽  
Structural Protein ◽  
Novel Coronavirus

Coronavirus belongs to the family of Coronaviridae, comprising single-stranded, positive-sense RNA genome (+ ssRNA) of around 26 to 32 kilobases, and has been known to cause infection to a myriad of mammalian hosts, such as humans, cats, bats, civets, dogs, and camels with varied consequences in terms of death and debilitation. Strikingly, novel coronavirus (2019-nCoV), later renamed as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and found to be the causative agent of coronavirus disease-19 (COVID-19), shows 88% of sequence identity with bat-SL-CoVZC45 and bat-SL-CoVZXC21, 79% with SARS-CoV and 50% with MERS-CoV, respectively. Despite key amino acid residual variability, there is an incredible structural similarity between the receptor binding domain (RBD) of spike protein (S) of SARS-CoV-2 and SARS-CoV. During infection, spike protein of SARS-CoV-2 compared to SARS-CoV displays 10–20 times greater affinity for its cognate host cell receptor, angiotensin-converting enzyme 2 (ACE2), leading proteolytic cleavage of S protein by transmembrane protease serine 2 (TMPRSS2). Following cellular entry, the ORF-1a and ORF-1ab, located downstream to 5′ end of + ssRNA genome, undergo translation, thereby forming two large polyproteins, pp1a and pp1ab. These polyproteins, following protease-induced cleavage and molecular assembly, form functional viral RNA polymerase, also referred to as replicase. Thereafter, uninterrupted orchestrated replication-transcription molecular events lead to the synthesis of multiple nested sets of subgenomic mRNAs (sgRNAs), which are finally translated to several structural and accessory proteins participating in structure formation and various molecular functions of virus, respectively. These multiple structural proteins assemble and encapsulate genomic RNA (gRNA), resulting in numerous viral progenies, which eventually exit the host cell, and spread infection to rest of the body. In this review, we primarily focus on genomic organization, structural and non-structural protein components, and potential prospective molecular targets for development of therapeutic drugs, convalescent plasm therapy, and a myriad of potential vaccines to tackle SARS-CoV-2 infection.

Stimulation of a major subset of lymphocytes expressing T cell receptor γδ by an antigen derived from mycobacterium tuberculosis

Cell ◽  
1989 ◽  
Vol 57 (4) ◽  
pp. 667-674 ◽  
Author(s):  
Rebecca L. O'Brien ◽  
Mary Pat Happ ◽  
Angela Dallas ◽  
Ed Palmer ◽  
Ralph Kubo ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Major Subset ◽  
Stimulation Of

scholarly journals Tuberculosis in Otorhinolaryngology: Clinical Presentation and Diagnostic Challenges

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Rajiv C. Michael ◽  
Joy S. Michael
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Pulmonary Tuberculosis ◽  
Clinical Presentation ◽  
Extrapulmonary Tuberculosis ◽  
Common Type ◽  
The Body ◽  
Diagnostic Challenge ◽  
Cervical Adenitis ◽  
Important Form

Tuberculosis affects all tissues of the body, although some more commonly than the others. Pulmonary tuberculosis is the most common type of tuberculosis accounting for approximately 80% of the tuberculosis cases. Tuberculosis of the otorhinolaryngeal region is one of the rarer forms of extrapulmonary tuberculosis but still poses a significant clinical and diagnostic challenge. Over three years, only five out of 121 patients suspected to have tuberculosis of the otorhinolaryngeal region (cervical adenitis excluded) hadMycobacterium tuberculosisculture-proven disease. Additional 7 had histology-proven tuberculosis. Only one patient had concomitant sputum-positive pulmonary tuberculosis. We look at the various clinical and laboratory aspects of tuberculosis of the otorhinolaryngeal region that would help to diagnose this uncommon but important form of extrapulmonary tuberculosis.

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