Transmembrane TNF and Its Receptors TNFR1 and TNFR2 in Mycobacterial Infections

Ruíz, Andy; Palacios, Yadira; García, Irene; Chávez‐Galán, Leslie

doi:10.3390/ijms22115461

Cited by 32 publications

(25 citation statements)

References 136 publications

(141 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The expression of tmTNF and tmTNFR1 on the CD3 + MDM subpopulations was differentially regulated in a virulence-dependent manner and mediated a proinflammatory microenvironment, which helps activate diverse functions that protect against Mtb infection through interactions with its receptors [ 6 ]. We evaluated the levels of solTNF, solTNFR1, and solTNFR2 produced by MDMs infected with H37Ra or H37Rv.…”

Section: Resultsmentioning

confidence: 99%

“…After an activation stimulus, tmTNF is proteolytically processed via the action of a disintegrin and metalloproteinase domain 17 to release the soluble form of TNF (solTNF). Both tmTNF and solTNF are bioactive molecules that function by interacting with their receptors, 1 or 2 (TNFR1 and TNFR2, respectively), which in turn can also be found in transmembrane or soluble forms [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Mycobacterium tuberculosis H37Rv Strain Increases the Frequency of CD3+TCR+ Macrophages and Affects Their Phenotype, but Not Their Migration Ability

Ramón‐Luing

Carranza

Téllez-Navarrete

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

In mycobacterial infections, the number of cells from two newly discovered subpopulations of CD3+ myeloid cells are increased at the infection site; one type expresses the T cell receptor (CD3+TCRαβ+) and the other does not (CD3+TCRαβ−). The role of Mycobacterium tuberculosis (Mtb) virulence in generating these subpopulations and the ability of these cells to migrate remains unclear. In this study, monocyte-derived macrophages (MDMs) infected in vitro with either a virulent (H37Rv) or an avirulent (H37Ra) Mtb strain were phenotypically characterized based on three MDM phenotypes (CD3−, CD3+TCRαβ+, and CD3+TCRαβ−); then, their migration ability upon Mtb infection was evaluated. We found no differences in the frequency of CD3+ MDMs at 24 h of infection with either Mtb strain. However, H37Rv infection increased the frequency of CD3+TCRαβ+ MDMs at a multiplicity of infection of 1 and altered the expression of CD1b, CD1c, and TNF on the surface of cells from both the CD3+ MDM subpopulations; it also modified the expression of CCR2, CXCR1, and CCR7, thus affecting CCL2 and IL-8 levels. Moreover, H37Rv infection decreased the migration ability of the CD3− MDMs, but not CD3+ MDMs. These results confirm that the CD3+ macrophage subpopulations express chemokine receptors that respond to chemoattractants, facilitating cell migration. Together, these data suggest that CD3+ MDMs are a functional subpopulation involved in the immune response against Mtb.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mycobacterium tuberculosis H37Rv Strain Increases the Frequency of CD3+TCR+ Macrophages and Affects Their Phenotype, but Not Their Migration Ability

Ramón‐Luing

Carranza

Téllez-Navarrete

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…Both TNF forms mediate diverse functions through interaction with its receptors, TNFR1 and TNFR2, which also are shed by the ADAM17 proteolytic action. Moreover, ADAM17 also mediates the shedding of angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV-2 [10,11].…”

Section: Introductionmentioning

confidence: 99%

Severe COVID-19 Patients Show an Increase in Soluble TNFR1 and ADAM17, with a Relationship to Mortality

Palacios

Ruíz

Ramón‐Luing

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

Overproduction of inflammatory cytokines is a keystone event in COVID-19 pathogenesis; TNF and its receptors (TNFR1 and TNFR2) are critical pro-inflammatory molecules. ADAM17 releases the soluble (sol) forms of TNF, TNFR1, and TNFR2. This study evaluated TNF, TNFRs, and ADAM17 at the protein, transcriptional, and gene levels in COVID-19 patients with different levels of disease severity. In total, 102 patients were divided into mild, moderate, and severe condition groups. A group of healthy donors (HD; n = 25) was included. Our data showed that solTNFR1 and solTNFR2 were elevated among the COVID-19 patients (p < 0.0001), without increasing the transcriptional level. Only solTNFR1 was higher in the severe group as compared to the mildly ill (p < 0.01), and the level was higher in COVID-19 patients who died than those that survived (p < 0.0001). The solTNFR1 level had a discrete negative correlation with C-reactive protein (p = 0.006, Rho = −0.33). The solADAM17 level was higher in severe as compared to mild disease conditions (p < 0.01), as well as in COVID-19 patients who died as compared to those that survived (p < 0.001). Additionally, a potential association between polymorphism TNFRSF1A:rs767455 and a severe degree of disease was suggested. These data suggest that solTNFR1 and solADAM17 are increased in severe conditions. solTNFR1 should be considered a potential target in the development of new therapeutic options.

show abstract

“…TNF is a trimeric molecule that can be found as a transmembrane (tmTNF) or soluble form (sTNF) by the action of ADAM17 [ 77 , 78 ]. Both forms are bioactive molecules after interacting with one of its receptors, TNFR1 or TNFR2 [ 77 , 79 ]. Importantly, the soluble formats of both receptors can also be generated by the sheddase activity of ADAM17.…”

Section: What Is Tnf and Its Inhibitors?mentioning

confidence: 99%

“…The use of anti-TNF therapy requires an integrative comprehension considering the roles of TNFR1 and TNFR2, as well as the soluble or transmembrane formats of the proteins [ 79 ]. Based on the discussed evidence, we suggest that the clinical trials to evaluate the efficiency of the anti-TNF therapy should do an integral association between levels of TNF and its receptors.…”

Section: Could Be Stnfr1 a Treatment Target For Covid-19?mentioning

confidence: 99%

Immunosuppressant Therapies in COVID-19: Is the TNF Axis an Alternative?

Palacios

Chávez‐Galán

2022

Pharmaceuticals

Self Cite

View full text Add to dashboard Cite

The study of cytokine storm in COVID-19 has been having different edges in accordance with the knowledge of the disease. Various cytokines have been the focus, especially to define specific treatments; however, there are no conclusive results that fully support any of the options proposed for emergency treatment. One of the cytokines that requires a more exhaustive review is the tumor necrosis factor (TNF) and its receptors (TNFRs) as increased values of soluble formats for both TNFR1 and TNFR2 have been identified. TNF is a versatile cytokine with different impacts at the cellular level depending on the action form (transmembrane or soluble) and the receptor to which it is associated. In that sense, the triggered mechanisms can be diversified. Furthermore, there is the possibility of the joint action provided by synergism between one or more cytokines with TNF, where the detonation of combined cellular processes has been suggested. This review aims to discuss some roles of TNF and its receptors in the pro-inflammatory stage of COVID-19, understand its ways of action, and let to reposition this cytokine or some of its receptors as therapeutic targets.

show abstract

Transmembrane TNF and Its Receptors TNFR1 and TNFR2 in Mycobacterial Infections

Cited by 32 publications

References 136 publications

Mycobacterium tuberculosis H37Rv Strain Increases the Frequency of CD3+TCR+ Macrophages and Affects Their Phenotype, but Not Their Migration Ability

Mycobacterium tuberculosis H37Rv Strain Increases the Frequency of CD3+TCR+ Macrophages and Affects Their Phenotype, but Not Their Migration Ability

Severe COVID-19 Patients Show an Increase in Soluble TNFR1 and ADAM17, with a Relationship to Mortality

Immunosuppressant Therapies in COVID-19: Is the TNF Axis an Alternative?

Contact Info

Product

Resources

About