TAM receptors: A phosphatidylserine receptor family and its implications in viral infections

Abstract Multiple Myeloma (MM) patients are strongly sensitive to bacterial, fungal and viral infections. Furthermore, MM is often newly diagnosed in the context of such infections. Given those recurrent infections remain a major cause of death of MM patients; we surmised that MM plasma-cells could be activated by microorganisms, therefore contributing to the initiation and progression of the disease. Microorganisms share highly conserved structures called pathogen-associated molecular patterns. They are recognized by a family of receptors that act as sensor for the innate immune system and are called the Toll-like receptor family (TLRs). We first measured the expression of the 10 known human TLRs on 16 human MM plasma-cells lines (HMCLs) and freshly purified Plasma-cells from 13 patients. The expression pattern is heterogeneous among HMCLs and does not correlate with the one of B cells. Indeed TLR-3, 4, and 8 are aberrantly expressed. On the contrary, the expression of TLR-2 and 10 is lost on most of the HMCLs. TLR-1, 7 and 9 are the most frequently expressed (15+/16, 12+/16 and 11+/16 respectively). Primary MM plasma-cells also express TLR-7 (9+/13) and TLR-9 (8+/13). Accordingly to this expression profile, culture with TLR-7 ligand (loxoribine) or TLR-9 ligand (hypomethylated DNA from bacteria) increased 1,7 to 6 times (mean 3 ± 1,4 n= 8) the proliferation of IL-6-dependent and independent HMCLs. Furthermore, we observed a resistance to serum-deprivation as well as to dexamethasone-induced apoptosis. Those effects were IL-6-mediated in IL-6-dependent HMCLs since a blocking antibody to IL-6 neutralized the growth and survival induced by TLR triggering. In conclusion, human MM Plasma-cells express a broad range of TLRs and the triggering of TLR-7 and 9 induces tumor cell growth and prevent chemotherapy-induced apoptosis. These effects are mediated by the induction of an autocrine loop of growth factors as IL-6, and others currently under identification in the case of IL-6 independent HMCLs. Thus, MM plasma-cells take advantage of infections to expand and escape to usual therapies.

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CD300 receptor family in viral infections

European Journal of Immunology ◽

10.1002/eji.201847951 ◽

2018 ◽

Vol 49 (3) ◽

pp. 364-374 ◽

Cited By ~ 10

Author(s):

Joana Vitallé ◽

Iñigo Terrén ◽

Ane Orrantia ◽

Olatz Zenarruzabeitia ◽

Francisco Borrego

Keyword(s):

Viral Infections ◽

Receptor Family

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Potential Role of Antioxidant and Anti-Inflammatory Therapies to Prevent Severe SARS-Cov-2 Complications

Antioxidants ◽

10.3390/antiox10020272 ◽

2021 ◽

Vol 10 (2) ◽

pp. 272

Author(s):

Anna M. Fratta Pasini ◽

Chiara Stranieri ◽

Luciano Cominacini ◽

Chiara Mozzini

Keyword(s):

Potential Role ◽

Viral Infections ◽

Host Cells ◽

Nuclear Factor ◽

Angiotensin Converting Enzyme 2 ◽

Pyrin Domain ◽

Nrf2 Activation ◽

Anti Inflammatory ◽

Receptor Family

The coronavirus disease 2019 (COVID-19) pandemic is caused by a novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2). Here, we review the molecular pathogenesis of SARS-CoV-2 and its relationship with oxidative stress (OS) and inflammation. Furthermore, we analyze the potential role of antioxidant and anti-inflammatory therapies to prevent severe complications. OS has a potential key role in the COVID-19 pathogenesis by triggering the NOD-like receptor family pyrin domain containing 3 inflammasome and nuclear factor-kB (NF-kB). While exposure to many pro-oxidants usually induces nuclear factor erythroid 2 p45-related factor2 (NRF2) activation and upregulation of antioxidant related elements expression, respiratory viral infections often inhibit NRF2 and/or activate NF-kB pathways, resulting in inflammation and oxidative injury. Hence, the use of radical scavengers like N-acetylcysteine and vitamin C, as well as of steroids and inflammasome inhibitors, has been proposed. The NRF2 pathway has been shown to be suppressed in severe SARS-CoV-2 patients. Pharmacological NRF2 inducers have been reported to inhibit SARS-CoV-2 replication, the inflammatory response, and transmembrane protease serine 2 activation, which for the entry of SARS-CoV-2 into the host cells through the angiotensin converting enzyme 2 receptor. Thus, NRF2 activation may represent a potential path out of the woods in COVID-19 pandemic.

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TAM receptors, Gas6, and protein S: roles in inflammation and hemostasis

Blood ◽

10.1182/blood-2013-09-528752 ◽

2014 ◽

Vol 123 (16) ◽

pp. 2460-2469 ◽

Cited By ~ 113

Author(s):

Jonathan H. M. van der Meer ◽

Tom van der Poll ◽

Cornelis van ‘t Veer

Keyword(s):

Tyrosine Kinases ◽

Protein C ◽

Protein S ◽

Coagulation Factors ◽

Receptor Activation ◽

Cell Type ◽

Primary Hemostasis ◽

Tam Receptors ◽

And Migration ◽

Receptor Family

Abstract TAM receptors (Tyro3, Axl, and Mer) belong to a family of receptor tyrosine kinases that have important effects on hemostasis and inflammation. Also, they affect cell proliferation, survival, adhesion, and migration. TAM receptors can be activated by the vitamin K–dependent proteins Gas6 and protein S. Protein S is more commonly known as an important cofactor for protein C as well as a direct inhibitor of multiple coagulation factors. To our knowledge, the functions of Gas6 are limited to TAM receptor activation. When activated, the TAM receptors have effects on primary hemostasis and coagulation and display an anti-inflammatory or a proinflammatory effect, depending on cell type. To comprehend the effects that the TAM receptors and their ligands have on hemostasis and inflammation, we compare studies that report the different phenotypes displayed by mice with deficiencies in the genes of this receptor family and its ligands (protein S+/−, Gas6−/−, TAM−/−, and variations of these). In this manner, we aim to display which features are attributable to the different ligands. Because of the effects TAM receptors have on hemostasis, inflammation, and cancer growth, their modulation could make interesting therapeutic targets in thromboembolic disease, atherosclerosis, sepsis, autoimmune disease, and cancer.

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The Diagnosis of Viral Disease by Electron Microscopy

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010005398x ◽

1982 ◽

Vol 40 ◽

pp. 270-273

Author(s):

William B. McCombs ◽

Cameron E. McCoy

Keyword(s):

Electron Microscopy ◽

Hospital Stay ◽

Viral Infections ◽

Medical Profession ◽

Bacterial Pathogens ◽

Viral Disease ◽

Viral Pathogens ◽

Academic Interest ◽

The Past

Recent years have brought a reversal in the attitude of the medical profession toward the diagnosis of viral infections. Identification of bacterial pathogens was formerly thought to be faster than identification of viral pathogens. Viral identification was dismissed as being of academic interest or for confirming the presence of an epidemic, because the patient would recover or die before this could be accomplished. In the past 10 years, the goal of virologists has been to present the clinician with a viral identification in a matter of hours. This fast diagnosis has the potential for shortening the patient's hospital stay and preventing the administering of toxic and/or expensive antibiotics of no benefit to the patient.

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Detection of Nucleic Acids in Cells or Tissue Sections Using In situ Polymerase Chain Reaction (PCR)

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100162545 ◽

1996 ◽

Vol 54 ◽

pp. 16-17

Author(s):

J. R. Hully ◽

K. R. Luehrsen ◽

K. Aoyagi ◽

C. Shoemaker ◽

R. Abramson

Keyword(s):

Nucleic Acids ◽

Viral Infections ◽

Anatomical Location ◽

Rt Pcr ◽

Reverse Transcription Pcr ◽

Cellular Source ◽

Gene Transcripts ◽

Initial Description ◽

In Cells

The development of PCR technology has greatly accelerated medical research at the genetic and molecular levels. Until recently, the inherent sensitivity of this technique has been limited to isolated preparations of nucleic acids which lack or at best have limited morphological information. With the obvious exception of cell lines, traditional PCR or reverse transcription-PCR (RT-PCR) cannot identify the cellular source of the amplified product. In contrast, in situ hybridization (ISH) by definition, defines the anatomical location of a gene and/or it’s product. However, this technique lacks the sensitivity of PCR and cannot routinely detect less than 10 to 20 copies per cell. Consequently, the localization of rare transcripts, latent viral infections, foreign or altered genes cannot be identified by this technique. In situ PCR or in situ RT-PCR is a combination of the two techniques, exploiting the sensitivity of PCR and the anatomical definition provided by ISH. Since it’s initial description considerable advances have been made in the application of in situ PCR, improvements in protocols, and the development of hardware dedicated to in situ PCR using conventional microscope slides. Our understanding of the importance of viral latency or viral burden in regards to HIV, HPV, and KSHV infections has benefited from this technique, enabling detection of single viral copies in cells or tissue otherwise thought to be normal. Clearly, this technique will be useful tool in pathobiology especially carcinogenesis, gene therapy and manipulations, the study of rare gene transcripts, and forensics.

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