Blog posts

TLR4 localization: Shaping inflammation is a battle of the lineages

By Dhiren Patel

Edited by Chloe Pyle and Faith Uwadiae

In the recent ‘Compare & Contrast’ journal club, we had the pleasure of discussing two excellent papers based on the immunopathological roles of Toll-like Receptor 4 (TLR4). The two papers presented the importance of the localisation of TLR4 on stromal or haematopoietic cell types and their contribution in inducing pathology in different airway disease models.

Toll-like receptor 4, is a pattern-recognition receptor that is expressed on array of cells and a common agonist for this receptor is Lipopolysaccharide (LPS), a sugar molecule highly expressed on gram negative bacterial cells1. The importance of TLR4 expression on immune cells such as granulocytes, neutrophils and eosinophils in driving an immune response against various pathogens has been published on extensively.

Chemokine cascades drive the education of metastasis-promoting macrophages

Written by Caroline Anderson

Edited by William Foster and Arunon Sivananthan

This week we were fortunate enough to welcome a world-renowned biomedical scientist to the IRD journal club. Professor Jeffrey Pollard is currently the Director of the Medical Research Council Centre for Reproductive Health at the University of Edinburgh. His seminar earlier in the day had focussed on the role of the tumour microenvironment, and metastasis-associated macrophages (MAMs) in particular, in breast cancer metastasis. Much of the work he discussed can be found here: Kitamura et al, JEM, 2015 (PMID: 26056232).

Both pro- and anti-tumorigenic immune cells are found in association with tumours.

Hold your nerve; a new way to halt MPN progression

Written by William Foster

Edited by Judith Secklehner

On Monday the 15th of February the NHLI welcomed Dr Simón Méndez-Ferrer for a lunchtime seminar. Dr Méndez-Ferrer has recently moved from Madrid to Cambridge, where he has established a group in the Haematology department. Dr Méndez-Ferrer studies the multisystem regulation of the haematopoietic stem cell niche and his work has clinical implications for bone marrow transplantation procedures, as well as insight into specific forms of leukaemia. In Simón’s talk he discussed haematopoietic stem cell trafficking; paying attention to the importance of microenvironments; with focus on the importance of neural signal modulation within the bone marrow and how Mesenchymal Stem cells(MSCs) regulate inflammatory cell trafficking.

Insights into the life cycle of filarial parasites

Written by William Branchett

Edited by John Mackey

IRD recently hosted Dr Coralie Martin from the Muséum National d’Histoire Naturelle in Paris, who led a seminar and Journal Club on her research of the dynamics of filarial parasite infection. Filariae are nematodes that can cause debilitating and disfiguring diseases such as river blindness, which affects around 37 million people in Africa. Dr Martin utilises the rodent filarial parasite Litomosoides (L.) sigmodontis in mouse models to identify novel strategies for intervention in filarial infection.

In her seminar, Dr Martin focused on the life cycle of L. sigmodontis, which begins by intradermal delivery of larvae via an insect bite.

Getting enough iron in their diet: macrophages develop specialized protective functions within atherosclerotic plaques

Written by Khansa Hussain

Edited by Caroline Anderson

Last November we had the pleasure to welcome Dr Joseph Boyle from Imperial College London to our IRD Journal Club. He nominated his publication “Activating Transcription Factor 1 Directs Mhem Atheroprotective Macrophages Through Coordinated Iron Handling and Foam Cell Protection” to introduce and discuss with us his interesting finding of identifying a unique state of macrophages (Mhem) within intraplaque hemorrhage (IPH). IPH is a common feature of atherosclerotic plaque damage which involves the rupture of neovessels causing blood to escape into the surrounding tissues. This leads to cholesterol and heme/iron loading. The monocytes that enter the plaques and differentiate to macrophages to clear hemorrhage-related iron or lipid are known as Mhem macrophages to discriminate them from the classic lipid-laden macrophages (foam cells).

Neutrophils know when to cast a wide NET

Written by Dhiren Patel

Edited by Judith Secklehner and John Mackey

We recently had the pleasure of attending a great seminar by Dr. Venizelos Papayannopoulos of the Francis Crick Institute titled “Decision making neutrophils in antimicrobial responses”.

He introduced the audience to Neutrophil Extracellular Traps (NETs) which are large web-like structures consisting of neutrophil cellular components post necrosis. NETs consist primarily of histones but also contain a large proportion of the potent arsenal of granular components that neutrophils commonly utilise to kill and digest pathogens.

Dr. Papatannopolous then introduced us to the first of 2 papers he discusses in the seminar titled “Neutrophils sense microbe size and selectively release neutrophil extracellular traps in response to large pathogens1”.

A retro approach to T cell expansion

By Faith Uwadiae

Edited by William Branchett

Recently we welcomed Professor Phillip Ashton-Rickardt for an insightful lecture and journal club discussion on his latest science paper, describing the identification of a novel protein important for T cell proliferation. (Read the full article here: https://www.sciencemag.org/content/348/6238/995.full)

Effective CD8+ T cells responses are required for robust control of viral infections. However, during chronic infections, including clone 13 lymphocytic choriomenigitis virus (LCMV Cl13), the CD8+ T cell response becomes exhausted resulting in viral persistence. Ashton-Rickardt and colleagues used a forward genetic chemical mutagenesis approach to generate a panel of mouse lines, which they screened for enhanced CD8+ T cell responses during LCMV Cl13 infection.

Interaction between S100A8/A9 with RAGE triggers a novel mechanism for NK cell activation

Written by Judith Secklehner

Edited by Faith Uwadiae

In our latest Journal Club session we discussed a recent publication in the Journal of Immunology. Narumi et al. investigated the role of S100A8/A9 (or Calprotectin) in a tumor environment and discovered a new role of this protein for NK cell activation via interaction with RAGE (receptor of advanced glycation end product).

The study focused on the heterodimeric protein calprotectin, which is formed of the two Ca2+-binding proteins S100A8 and S100A9. Calprotectin can be found in the cytosol of myeloid cells, but not in lymphocytes. Many intracellular and extracellular proinflammatory functions are attributed to calprotectin, essentially regulation of leukocyte adhesion and migration and promotion of cytokine production.  Although it can also act as an oxidant scavenger and possesses antimicrobial activity against bacteria and fungi.

CD8+ T cells follow neutrophil snail trails in virus-infected airways

Written by Caroline Anderson

Edited by John MacKey

The focus of our journal club this week was a recent paper from Science describing a novel mechanism by which neutrophils deposit chemokine-enriched way-markers to guide CD8+ T cells to the airways during influenza virus infection. (read the full article here http://www.sciencemag.org/content/349/6252/aaa4352.full).

Photo: Krstnn Hrmnsn, Creative Commons License

Whilst the role of chemokines in attracting effector immune cells to sites of immune insult is well established, how localized chemokine gradients are produced and maintained is incompletely understood. Likewise, the molecular mechanisms linking neutrophils and T cell recruitment in viral infections is unclear.

Influenza Promotes Collagen Deposition via αvβ6 Integrin-mediated Transforming Growth Factor β Activation

Journal club with Gisli Jenkins from 21/9/15

Written by David Salman, Richard Toshner and Joana Alçada

Edited by Sarah Allden

We recently welcomed Dr Gisli Jenkins, Clinical Associate Professor & Reader in Pulmonary Biology from the University of Nottingham to the IRD Journal Club.

His recent publication “Influenza Promotes Collagen Deposition via αvβ6 Integrin-mediated Transforming Growth Factor β Activation” served as a starting point to discuss various aspects of research in lung fibrosis. The paper explores the relationship between influenza and idiopathic pulmonary fibrosis via transforming growth factor β (TGF-β), a cytokine involved in development, inflammation and wound repair.

The authors hypothesised that influenza-induced epithelial cell damage would stimulate toll-like receptor 3 (TLR3) activity, a receptor that recognizes by-products from viruses such as influenza.