Mahdad Noursadeghi

In @elife.bsky.social: Type I interferon responses contribute to immune protection against mycobacterial infection doi.org/10.7554/eLif...
#TBSky #IDSky #Immunosky
work led by Gillian Tomlinson with support from @mnoursad.bsky.social & @innate2adaptive.bsky.social group (1/5)

Very excited to share our new piece of work in the Lancet Global Health @lancetgh.bsky.social – Periskope-CM, a set of personalised risk prediction tools for HIV-associated cryptococcal meningitis mortality: www.thelancet.com/journals/lan...
#IDsky #HIV #GlobalHealth #meningitis #fungal
1/8

Come on down, anyone eligible for a post-doc do consider applying for this exciting project with @jennyrohn.bsky.social, @scottishwormboy.bsky.social & me!

Got a touch of #UTISky #IDSky #ImmunoSky & 🧪 about it! 😉

We also hope Metaclonotypist will prove to be a valuable application for fast and flexible parameter optimisation for identification of T cell metaclones across wide-ranging disease domains.

Given the critical role of T cell immunity in TB, we are excited about the potential for using generalisable T cell metaclones for improved disease-risk stratification in Mtb-infected people, and for identification of T cell epitopes for development of more effective vaccines.

Although the predominant repertoire of T cell reactivity to Mtb epitopes is private to individuals, we found striking evidence for population-wide immunodominance at the level of individual pMHC specificity revealed by highly generalisable/public T cell metaclones.

To overcome inter-individual TCR sequence diversity for shared peptide-MHC specific responses to Mtb , we developed a new computational pipeline, Metaclonotypist, to identify HLA-associated clusters of similar TCR sequences (metaclones) across a large ethnically diverse study population.

We used the tuberculin skin test as a standardised in vivo challenge comprising the whole Mtb proteome to generate localised enrichment of Mtb reactive T cells derived from the whole in vivo repertoire, which we characterised by TCR sequencing.

Evolution of T cell responses in the tuberculin skin test reveals generalisable Mtb-reactive T cell metaclones. T cells contribute to immune protection and pathogenesis in tuberculosis, but measurements of polyclonal responses have failed to resolve correlates of outcome. We report the first temporal…

Interested in T cell immunity in TB? Check out our new pre-print on antigen-agnostic identification of generalisable human in vivo Mtb-reactive T cell responses: www.biorxiv.org/content/10.1...
with @qimmuno.bsky.social & @innate2adaptive.bsky.social

Dr Munyaradzi Musvosvi speaks about the Titan Vaccine Research Project which will allow selection of most promising TB vaccine candidates. This work is supported by the South African mRNA Vaccine Consortium & funded by @samrcza.bsky.social @tomscriba.bsky.social www.youtube.com/watch?v=zwPM...

YouTube video by SATVIUCT Immunopathology of TB: Studying the role of the lymph nodes in the TB spectrum.

Immunopathology of TB: SATVI researchers discuss a groundbreaking study which investigates the role of lymph nodes in the context of mycobacterium tuberculosis infection and disease. The study was funded by a grant from
@wellcomeleap.bsky.social a program of youtu.be/8_gCOAfWUpw

2 weeks to the deadline for applications to this post.. take a look, get in touch if you want hear more, don't hold back😎

World Immunization Week 2025 World Immunization Week, celebrated in the last week of April, aims to promote the life-saving power of immunization to protect people of all ages against vaccine-preventable diseases. Vaccines are on...

It's just under 1 month to World Immunisation Week 2025 (24th - 30th April)! Check the link below to read more about this crucial campaign for global health.

www.who.int/campaigns/wo...

#WorldImmunisationWeek #VaccinesWork #WHO

A logo showing a person and the words Be Part of Research

Academic Clinical Lecturer Posts in Infection now out: for people training in ID in UK & hold/imminently completing PhD.

2 posts @lshtm.bsky.social
shorturl.at/EIUIz

1 at St Georges & 1 at Kings
shorturl.at/8kDY3

If interested in @lshtm.bsky.social posts get in touch.
UK ID people please share!!

We’re hiring! Looking for a laboratory post-doc fellow to help us disentangle protective and pathogenic T cells in TB, so we can stratify disease-risk after infection, and develop more effective vaccines. Interdisciplinary science in the heart of London. What's not to like? More here: bit.ly/4iIEiwu

This is a great initiative!

Fab analysis @hannahrickman.bsky.social - will we be well cited. are there sex-stratified data for house-hold contacts for which we may expect similar exposures?

State of the art in the enigmatic and complex world of immunological determinants of TB👇

Graphical summary of our paper. In mice, prior lower airway exposure to diverse inflammatory stimuli, including chronic bacterial infections such as M. tuberculosis, acute bacterial infections such as pulmonary S. aureus, viral infections such as Influenza A, type-II allergic responses such as the OVA-Alum model, activation of pulmonary TLR9 by CpG or pulmonary TLR1/2 by Pam3CSK4 leads to reduced viral burden upon subsequent infection with SARS-CoV-2 (SCV2). (2) This SCV2 restriction occurs prior to induction of SCV2-specific adaptive immune responses and is mediated through innate immune responses, including the induction of IFN-I, TNFα and IL-1 and sustained changes to the TRM (Tissue resident macrophage) cellular compartment and the pulmonary epithelium. (3) Innate cytokine and TLR signaling to both recruited immune cells and the pulmonary epithelium creates a microenvironment in the lung that limits early replication of SCV2. IFN-I signaling to pulmonary ECs (epithelial cells) increases expression of interferon-stimulated genes, that likely cell-intrinsically limit viral replication. TNF- or IL-1 suppress SCV2 independently of IFN-I signaling. TNF acts exclusively through radio-resistant cell types such as the lung epithelium, whereas IL-1 affords control both direct and indirectly, through either stromal and hematopoietic cell types, to restrict overall early SCV2 burden.

Best #Nikolaus 🎅! Our paper on how the 🫁 microenvironment can shape #innate immunity against #viruses is out @sciimmunology.bsky.social This was a herculean effort brilliantly led by @pauljbaker.bsky.social who singlehandedly established the model in the lab during the pandemic. 🧪 #Immunosky 1/9

Exciting- live to hear more!

important point- have not done this yet- wonder whether protein as dynamic as transcripts

and these data from unselected acute respiratory viruses in community acquired infection - with longitudinal sampling after the symptom onset

Not sure if I have misunderstood- our findings that distinct biomarkers discriminate early & late phases of infection were generalisable to all acute respiratory viruses we have been able to test - panel on right = extended time course from Flu challenge

SARS-CoV-2 Human Challenge Studies — Establishing the Model during an Evolving Pandemic | NEJM While commentators have made theoretical arguments for and against SARS-CoV-2 challenge studies, a consortium of academics, industry collaborators, and the British government has proceeded to addre...

Obviously super important consideration -debated extensively - for interest, some more commentary and reflections here: www.nejm.org/doi/10.1056/...

SARS-CoV-2 Human Challenge Studies — Establishing the Model during an Evolving Pandemic | NEJM While commentators have made theoretical arguments for and against SARS-CoV-2 challenge studies, a consortium of academics, industry collaborators, and the British government has proceeded to addre...

Debated extensively then and now - for interest, some commentary and reflections here: www.nejm.org/doi/10.1056/...

Human SARS-CoV-2 challenge uncovers local and systemic response dynamics - Nature A human SARS-CoV-2 challenge study in individuals without previous exposure to the virus or vaccines provides detailed profiles of local and systemic epithelial and immune cell response dynamics over ...

www.nature.com/articles/s41...

Mucosal and systemic immune correlates of viral control after SARS-CoV-2 infection challenge in seronegative adults We present an in-depth analysis of mucosal and systemic immune responses after SARS-CoV-2 challenge infection of seronegative adults.

www.science.org/doi/10.1126/...

Viral emissions into the air and environment after SARS-CoV-2 human challenge: a phase 1, open label, first-in-human study After controlled experimental inoculation, the timing, extent, and routes of viral emissions was heterogeneous. We observed that a minority of participants were high airborne virus emitters, giving su...

www.thelancet.com/journals/lan...

Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults - Nature Medicine In the first SARS-CoV-2 challenge study in humans, 36 young, healthy adult participants were intranasally inoculated with virus and monitored for productive infection, symptoms, virus kinetics, antibo...

Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults: www.nature.com/articles/s41...

this discovery would not have been possible without the detailed time course sampling anchored in a standardised experimental challenge ... as you rightly say lot's of other insights from this model - for convenience, links to these below: