scholarly journals Opposing roles of endosomal innate immunity proteins IFITM3 and TLR7 in human metapneumovirus infection

2018 ◽  
Author(s):  
Temet M. McMichael ◽  
Yu Zhang ◽  
Adam D. Kenney ◽  
Lizhi Zhang ◽  
Mijia Lu ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Plasma Membrane ◽  
Transmembrane Protein ◽  
Human Metapneumovirus ◽  
Toll Like Receptor ◽  
Entry Pathway ◽  
Hmpv Infection ◽  
Cellular Factors ◽  
Entry Strategy ◽  
Cellular Entry

ABSTRACTHuman metapneumovirus (hMPV) utilizes a bifurcated cellular entry strategy, fusing either with the plasma membrane or, after endocytosis, with the endosome membrane. Whether cellular factors restrict or enhance either entry pathway is largely unknown. We found that the interferon-induced transmembrane protein 3 (IFITM3) inhibits hMPV infection to an extent similar to endocytosis-inhibiting drugs, and an IFITM3 variant that accumulates at the plasma membrane in addition to its endosome localization provided increased virus restriction. Mechanistically, IFITM3 blocks hMPV F protein-mediated membrane fusion, and inhibition of infection was reversed by the membrane destabilizing drug amphotericin B. Conversely, we unexpectedly found that infection by some hMPV strains is enhanced by Toll-like receptor 7 (TLR7), an endosomal protein, suggesting that cellular entry via endocytosis may be particularly advantageous for hMPV despite eventual restriction of this pathway upon induction of IFITM3. Overall, our results identify IFITM3 and TLR7 as endosomal factors differentially regulating hMPV infection.

scholarly journals The contribution of miR-122 to the innate immunity by regulating toll-like receptor 4 in hepatoma cells

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Liyu Shi ◽  
Xiaoqiu Zheng ◽  
Yuzhuo Fan ◽  
Xiaolan Yang ◽  
Aimei Li ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Hepatoma Cells ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4

scholarly journals Lateral diffusion of wild-type and mutant Ld antigens in L cells.

1984 ◽  
Vol 99 (6) ◽  
pp. 2333-2335 ◽  
Author(s):  
M Edidin ◽  
M Zuniga
Keyword(s):  
Plasma Membrane ◽  
Diffusion Coefficients ◽  
Transmembrane Protein ◽  
Transmembrane Proteins ◽  
Lateral Diffusion ◽  
Cytoplasmic Domain ◽  
Histocompatibility Antigen ◽  
Wild Type ◽  
Major Histocompatibility Antigen ◽  
Cytoplasmic Side

We have compared the lateral diffusion of intact transmembrane proteins, wild-type H-2Ld antigens, with that of mutants truncated in the cytoplasmic domain. Diffusion coefficients and mobile fractions were similar for all molecules examined, from wild-type Ld antigens with 31 residues on the cytoplasmic side of the plasma membrane to mutants with only four residues in the cytoplasmic domain. This result limits ways in which the lateral diffusion of a major histocompatibility antigen, a transmembrane protein, can be constrained by interactions with other molecules.

scholarly journals Toll-like receptor 4 ablation in mdx mice reveals innate immunity as a therapeutic target in Duchenne muscular dystrophy

2014 ◽  
Vol 24 (8) ◽  
pp. 2147-2162 ◽  
Author(s):  
Christian Giordano ◽  
Kamalika Mojumdar ◽  
Feng Liang ◽  
Christian Lemaire ◽  
Tong Li ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Therapeutic Target ◽  
Mdx Mice ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4

scholarly journals Regiospecific Methylation of a Dietary Flavonoid Scaffold Selectively Enhances IL-1β Production following Toll-like Receptor 2 Stimulation in THP-1 Monocytes

2013 ◽  
Vol 288 (29) ◽  
pp. 21126-21135 ◽  
Author(s):  
Eng-Kiat Lim ◽  
Paul J. Mitchell ◽  
Najmeeyah Brown ◽  
Rebecca A. Drummond ◽  
Gordon D. Brown ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Natural Products ◽  
Intestinal Microflora ◽  
Rank Order ◽  
Inflammasome Activation ◽  
Toll Like Receptor ◽  
Immune Health ◽  
Toll Like Receptor 2 ◽  
Dietary Flavonoid ◽  
The Impact

It is now recognized that innate immunity to intestinal microflora plays a significant role in mediating immune health, and modulation of microbial sensing may underpin the impact of plant natural products in the diet or when used as nutraceuticals. In this context, we have examined five classes of plant-derived flavonoids (flavonols, flavones, flavanones, catechins, and cyanidin) for their ability to regulate cytokine release induced by the Toll-like receptor 2 (TLR2) agonist Pam3CSK4. We found that the flavonols selectively co-stimulated IL-1β secretion but had no impact on the secretion of IL-6. Importantly, this costimulation of TLR2-induced cytokine secretion was dependent on regiospecific methylation of the flavonol scaffold with a rank order of quercetin-3,4′-dimethylether > quercetin-3-methylether > casticin. The mechanism underpinning this costimulation did not involve enhanced inflammasome activation. In contrast, the methylated flavonols enhanced IL-1β gene expression through transcriptional regulation, involving mechanisms that operate downstream of the initial NF-κB and STAT1 activation events. These studies demonstrate an exquisite level of control of scaffold bioactivity by regiospecific methylation, with important implications for understanding how natural products affect innate immunity and for their development as novel immunomodulators for clinical use.

scholarly journals Cell-Mediated Responses to Human Metapneumovirus Infection

Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 542
Author(s):  
Marlies Ballegeer ◽  
Xavier Saelens
Keyword(s):  
Immune Response ◽  
Rna Virus ◽  
Cell Types ◽  
Host Immune Response ◽  
Human Metapneumovirus ◽  
Comprehensive Overview ◽  
Hmpv Infection ◽  
Life Threatening ◽  
Tract Infections ◽  
Almost All

Viruses are the most common cause of acute respiratory tract infections (ARTI). Human metapneumovirus (hMPV) frequently causes viral pneumonia which can become life-threatening if the virus spreads to the lungs. Even though hMPV was only isolated in 2001, this negative-stranded RNA virus has probably been circulating in the human population for many decades. Interestingly, almost all adults have serologic evidence of hMPV infection. A well-established host immune response is evoked when hMPV infection occurs. However, the virus has evolved to circumvent and even exploit the host immune response. Further, infection with hMPV induces a weak memory response, and re-infections during life are common. In this review, we provide a comprehensive overview of the different cell types involved in the immune response in order to better understand the immunopathology induced by hMPV. Such knowledge may contribute to the development of vaccines and therapeutics directed against hMPV.

scholarly journals A case–control study of innate immunity pathway gene polymorphisms in Puerto Ricans reveals association of toll-like receptor 2 +596 variant with asthma

2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Mario G. Ortiz-Martínez ◽  
Orquídea Frías-Belén ◽  
Sylvette Nazario-Jiménez ◽  
María López-Quintero ◽  
Rosa I. Rodríguez-Cotto ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Gene Polymorphisms ◽  
Case Control Study ◽  
Puerto Ricans ◽  
Case Control ◽  
Toll Like Receptor ◽  
Pathway Gene ◽  
Toll Like Receptor 2 ◽  
Innate Immunity Pathway ◽  
Control Study
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