Absence of Tumor Necrosis Factor Supports Alternative Activation of Macrophages in the Liver after Infection with Leishmania major.
S Hu,Cameron Marshall,Jocelyn M. Darby,Wei Wei,Alan Bruce Lyons,Heinrich Körner,Heinrich Körner +6 more
TLDR
The results support the notion of a general role of TNF in the inflammatory activation of macrophages and define a new role of IL-6 signaling in macrophage polarization downstream of TNP, as well as supporting the notion that IL- 6 could be involved in M2 differentiation.Abstract:
The absence of tumor necrosis factor (TNF) causes lethal infection by Leishmania major in normally resistant C57BL/6J (B6.WT) mice. The underlying pathogenic mechanism of this fatal disease has so far remained elusive. We found that B6.WT mice deficient for the tnf gene (B6.TNF-/-) displayed not only a non-healing cutaneous lesion but also a serious infection of the liver upon L. major inoculation. Infected B6.TNF-/- mice developed an enlarged liver that showed increased inflammation. Furthermore, we detected an accumulating monocyte-derived macrophage population (CD45+F4/80+CD11bhiLy6Clow) that displayed a M2 macrophage phenotype with high expression of CD206, arginase-1, and IL-6, supporting the notion that IL-6 could be involved in M2 differentiation. In in vitro experiments, we demonstrated that IL-6 upregulated M-CSF receptor expression and skewed monocyte differentiation from dendritic cells to macrophages. This was countered by the addition of TNF. Furthermore, TNF interfered with the activation of IL-6-induced gp130-signal transducer and activator of transcription (STAT) 3 and IL-4-STAT6 signaling, thereby abrogating IL-6-facilitated M2 macrophage polarization. Therefore, our results support the notion of a general role of TNF in the inflammatory activation of macrophages and define a new role of IL-6 signaling in macrophage polarization downstream of TNF.read more
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Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases.
Daniela Parada Venegas,Marjorie De la Fuente,Glauben Landskron,María-Julieta González,Rodrigo Quera,Gerard Dijkstra,Hermie J. M. Harmsen,Klaas Nico Faber,Marcela A. Hermoso +8 more
TL;DR: An overview of microbial SCFAs production and their effects on the intestinal mucosa with specific emphasis on their relevance for Inflammatory Bowel Diseases is presented and the therapeutic potential ofSCFAs for IBD is discussed.
Journal ArticleDOI
COVID-19 vaccine development and a potential nanomaterial path forward.
Matthew D Shin,Sourabh Shukla,Young Hun Chung,Veronique Beiss,Soo Khim Chan,Oscar A Ortega-Rivera,David M. Wirth,Angela Chen,Markus Sack,Jonathan K. Pokorski,Nicole F. Steinmetz +10 more
TL;DR: Current approaches to COVID-19 vaccine development are highlighted, highlighting the role of nanotechnology, manufacturing and distribution and a successful vaccine platform must enable rapid discovery, scalable manufacturing and global distribution.
Journal ArticleDOI
Roles of IFN-γ in tumor progression and regression: a review.
TL;DR: The current knowledge concerning the roles of IFN-γ in the TME as a part of the complex immune response to cancer is discussed and the importance of identifying IFn-γ responsive patients to improve their sensitivity to immuno-therapies is highlighted.
Journal ArticleDOI
Mucosal vaccines - fortifying the frontiers.
Ed C. Lavelle,Ross W. Ward +1 more
TL;DR: Mucosal vaccines offer the potential to trigger robust protective immune responses at the predominant sites of pathogen infection as discussed by the authors, which has the capacity to prevent an infection from becoming established in the first place, rather than only curtailing infection and protecting against the development of disease symptoms.
Journal ArticleDOI
Antiviral peptides as promising therapeutic drugs
Liana Costa Pereira Vilas Boas,Marcelo Lattarulo Campos,Marcelo Lattarulo Campos,Rhayfa Lorrayne Araujo Berlanda,Natan de Carvalho Neves,Octavio L. Franco,Octavio L. Franco,Octavio L. Franco +7 more
TL;DR: This review aims to shed some light on antimicrobial peptides with antiviral activities against human viruses and update the data about the already well-known peptides that are still undergoing studies, emphasizing the most promising ones that may become medicines for clinical use.
References
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