The concept of structural immunity, as defined in this Perspective, posits that the first line of immune defence against foreign agents and tissue damage involves the preventative, physical reinforcement of tissue barriers and that this fundamental task can be directly or indirectly regulated by immune cells. Indeed, several types of leukocytes can help build protective barriers when required, potentially either by depositing matrix components themselves in certain circumstances or, more generally, by interactions with canonical structural cells and the existing extracellular matrix. This concept of structural functions of immune cells challenges the rigidity with which mammalian tissue organization and immune defence have been traditionally compartmentalized. Although there is strong momentum in the evidence for structural immunity that has been acquired so far, the field lacks a comprehensive overview of these data as well as a critical evaluation of this concept. Here, we place independent findings from several groups into a working model of immune cells as the architects of tissue barriers, to present a framework on which new concepts and findings in this area can develop. This Perspective presents a framework of ‘structural immunity’ that positions immune cells as architects of tissue structure. Beyond their roles in antimicrobial defence, we posit that immune cells contribute to tissue homeostasis by guiding structural composition and, in some cases, directly building barrier components.

⚘️En 2008, la biologiste Katie Hinde a découvert quelque chose que la science avait ignoré pendant des siècles : le lait maternel n’est pas une recette fixe, c’est un message en perpétuel changement.

En étudiant des macaques en Californie, Hinde remarqua un motif étrange. Si la mère avait un petit mâle, son lait était plus épais, riche en graisses et en protéines (un carburant à haut indice d’octane). Si elle avait une petite femelle, le lait était plus abondant et chargé en calcium. Comment le corps de la mère savait-il modifier la formule chimique selon le sexe du bébé ?

Cela l’a conduite à découvrir le mécanisme le plus fascinant de la biologie humaine : le « flux rétrograde ».

Pendant des années, nous avons cru que le lait allait dans une seule direction (de la mère à l’enfant). Nous avions tort. Lorsqu’un bébé tète, le vide créé aspire une petite quantité de salive du bébé à l’intérieur du mamelon de la mère.
C’est là que se produit la magie : le tissu mammaire analyse cette salive. C’est un scanner biologique.

Si la salive contient des signaux indiquant que le bébé a de la fièvre ou une infection, le corps de la mère commence à fabriquer des anticorps spécifiques à cette maladie en quelques heures.

Si le bébé est stressé, le lait modifie ses niveaux hormonaux (comme le cortisol) pour influencer son tempérament.
Le lait change entre le matin et le soir. Il change si le bébé est malade. Il change selon qu’il est garçon ou fille.

Comme l’a conclu Hinde : « Le lait maternel est nourriture, médicament et signal ». C’est le système de communication le plus sophistiqué de la nature, une conversation silencieuse entre deux corps que même la technologie moderne n’a pas encore réussi à reproduire entièrement.

Validation historique et scientifique, Katie Hinde, PhD – Laboratoire de lactation comparée, Arizona State University.

vanhille.fr | 100 comments on LinkedIn

Gut Phageome: A New Frontier for Clinicians

A new Nature study using long-read metagenomics reveals that the human gut microbiome is far more dynamic than we thought

https://lnkd.in/dnVnetzX

Most gut bacteriophages (phages) are integrated in bacterial genomes, but a meaningful fraction are gained, lost, or even jump across bacterial species over time.

This means the gut microbiome is not just a community of bacteria - it’s an evolving genetic ecosystem shaped by phage–bacteria interactions.

Why it matters for clinical practice

Emerging evidence suggests that phage dynamics can influence:

• microbiome stability and dysbiosis
• inflammation and immune tone
• responses to antibiotics, diet, and microbiome-targeted therapies

Phage-aware diagnostics and therapeutics (including targeted phage cocktails) are already entering early clinical and translational research.

Take-home for clinicians:

1. The virome matters: Gut phages may become essential in interpreting microbiome results and understanding dysbiosis.

2. Therapies will evolve: Next-generation probiotics, FMT, and phage therapy will likely consider phage–bacteria interactions.

3. Expect personalization: Phage patterns may soon help stratify patients and guide individualized microbiome interventions.

Understanding the phageome is becoming a key part of understanding our gut

I believe this is one of the most important papers in microbiome science.

This new review in Neuron (Mitchell et al, 2025) systematically dismantles the gut microbiome-autism hypothesis through a critical assessment of published papers.

I was honestly shocked by the numbers: Despite 100+ papers per year and $20-25M in annual NIH funding since 2018, the most cited studies have tiny sample sizes (n=20 for some), uncorrected multiple testing, and contradictory findings. Some report higher microbial diversity in autism, others lower, many find no difference. The taxa they report are inconsistent. When properly analyzed with sibling controls and adequate statistical power, associations largely disappear.

The mouse model data is equally troubling. For example, a 2019 Cell paper claimed fecal transplants from autistic donors induced "autism-like behaviors" in mice. But when reanalyzed with proper statistics, the effects vanished. And it is really not clear how mouse behavior can model human autism.

And these are not obscure papers - they are published in the most high profile journals and have thousands of citations each.

Maybe it is not surprising that randomized controlled trials of probiotics show no consistent benefit for autism.

As a result, we're watching well-intentioned science fuel a billion dollar "wellness" industry selling unproven interventions to vulnerable families.

As a microbiome scientist, this really troubles me. Excellent research IS being done, and the microbiome holds real promise as a diagnostic and therapeutic tool. But these overhyped, methodologically weak studies cast a shadow over our entire field.

The solution, in my opinion – and completely I agree with the authors on this – is to adopt the rigor that transformed human genomics: pre-specified hypotheses, adequate power, standardized protocols and pipelines, large sample sizes, statistical robustness, replication, and above all: resisting the hype machine.

#microbiome #autism #scientificrigor #reproducibility #clinicaltrials | 36 comments on LinkedIn

The Gram-negative bacterium Bordetella pertussis causes whooping cough (pertussis), a severe respiratory disease, especially in young children, which is resurgent despite high vaccine coverage. The current acellular pertussis vaccine prevents severe disease but does not prevent nasal infection with B. pertussis. This parenterally delivered vaccine induces potent circulating antibody responses but limited respiratory tissue-resident memory T cells and IgA responses. Here we developed a vaccine approach based on respiratory delivery of antibiotic-inactivated B. pertussis (AIBP). Ciprofloxacin-treated B. pertussis potently activated antigen-presenting cells to drive T cell responses. AIBP immunization via aerosol or intranasal administration conferred a high level of protection against lung and nasal infection. The AIBP vaccine induced B. pertussis-specific interleukin (IL)-17-producing CD4 tissue-resident memory T cells that recruited neutrophils to the respiratory tract. Protection was abrogated by depletion of CD4 T cells or neutralization of IL-17 in mice. Unlike a parenterally delivered whole-cell pertussis vaccine, which induced high levels of serum IL-1β, IL-6, tumour necrosis factor and C-reactive protein, aerosol immunization with the AIBP vaccine did not promote systemic pro-inflammatory responses. We present preclinical evidence of a safe and effective respiratory-delivered vaccine platform for inducing T cell-mediated sterilizing immunity against a respiratory pathogen. In this preclinical study, the authors find that respiratory immunization with an antibiotic-treated bacterial vaccine is a highly effective approach for inducing tissue-resident memory T cells that protect against lung and nasal infection with Bordetella pertussis.

A team of Trinity College Dublin researchers has developed a new form of vaccine that could transform how we are protected from respiratory infections and reduce the chance of passing on whooping cough.

It could mean a whooping cough vaccine, currently given by way of injection, could be administered nasally to children and young ­babies whose lives are more at risk from the disease.

The research was led by Prof Kingston Mills (pictured) and Dr Seyed Davoud Jazayeri from the college's School of Biochemistry and Immunology. “We’ve applied our understanding of protective immune pathways to engineer a fundamentally different kind of vaccine. By stimulating immunity where infections begin, we can offer stronger protection and potentially interrupt community transmission,” Prof Mills said

Whoopingcough can sound like an old fashioned disease but Ireland has had a resurgence in whooping cough, with a record 713 cases reported last year. More than one in four of those infected needed hospital treatment.

The landmark study, published in Nature Microbiology, found the experimental vaccine in pre-clinical studies managed complete protection against infection of the lungs and nasal cavity. The research was initially funded through a Research Ireland and is now advancing under the Arc Hub for Therapeutics.

Read a summary here: https://lnkd.in/e8XcN3RF

Read the full story here: https://lnkd.in/e_wnmS-E

IBS, Irritable Bowel Syndrome, is a common gastrointestinal disorder, more common, in women, with symptoms such as abdominal pain, constipation or diarrhea. The cause of the disease is not clear, but the intestinal environment including the gut microbiota and serotonin appear to be important...

Crypt hyperplasia is a key feature of celiac disease and several other small intestinal inflammatory conditions. Analysis of the gut epithelial crypt zone by mass spectrometry-based tissue proteomics revealed a strong interferon-γ (IFN-γ) signal in active celiac disease.

Airway mucus has a crucial role in protecting against inhaled pathogens and regulating water homeostasis, but it can also diminish the efficacy of therapeutic pulmonary delivery. Recent development in inhalable materials and biologics has introduced strategies to modify mucus properties, strengthening mucosal protection, advancing drug delivery and targeting and supporting effective water regulation. In this Review, we thoroughly examine the structure and function of airway mucus, along with the challenges and opportunities it presents for inhaled treatments. We explore new methods that enhance the protective role of mucus through physical reinforcement, pathogen neutralization, muco-trapping and rehydration, as well as strategies that overcome the mucus barrier to improve drug delivery, including physical modulation, mucoadhesive design, muco-penetrating design, mucolytics and active targeting. Finally, we discuss the clinical implications of these promising strategies, emphasizing the need to balance mucosal function with optimized therapeutic delivery. We seek to explore prospective ways to improve inhalation therapies for both infectious and chronic lung diseases by reviewing recent progress in inhalable materials and biologics. Airway mucus complicates treatment of respiratory disease by both defending the lungs and hindering inhaled drugs to cross the barriers. This Review explores translational advances in inhalable materials and biologics that enhance mucus protection or drug penetration.

“A fog droplet isn’t a bad environment to live in"

We are proud to share newly published work from the Sjögren’s Foundation led by Foundation authors Kristie Cox, PhD and Matt Makara, MPH, now available in the Journal of Dental Research.
 
This review examines the connection between oral pathology and systemic disease in Sjögren’s disease, the current challenges in diagnosis and treatment, and the importance of integrated models of care that address both oral and systemic manifestations.
 
Highlights from the publication:
• A strong connection between oral pathology and systemic disease, including neuropathies, exists with Sjögren’s disease
• Current diagnostic and treatment paradigms are insufficient and there is a need for advanced and integrated approaches
• A multidisciplinary and patient centered model may improve outcomes and quality of life
 
Read the abstract:
https://lnkd.in/e2iBfjcg

See Figure 1 from the article on Salivary Gland Pathophysiology:
https://lnkd.in/eQaQUSjD

𝗡𝗲𝘄 𝗥𝗲𝘀𝗲𝗮𝗿𝗰𝗵: 𝗧 𝗰𝗲𝗹𝗹𝘀 𝗶𝗻 𝘁𝗶𝘀𝘀𝘂𝗲𝘀 𝗱𝗶𝗳𝗳𝗲𝗿 𝗺𝗮𝗿𝗸𝗲𝗱𝗹𝘆 𝗳𝗿𝗼𝗺 𝘁𝗵𝗼𝘀𝗲 𝗶𝗻 𝗯𝗹𝗼𝗼𝗱 - 𝗿𝗲𝘀𝗵𝗮𝗽𝗶𝗻𝗴 𝗵𝗼𝘄 𝘄𝗲 𝗲𝘃𝗮𝗹𝘂𝗮𝘁𝗲 𝘃𝗮𝗰𝗰𝗶𝗻𝗲𝘀 𝗮𝗻𝗱 𝗶𝗺𝗺𝘂𝗻𝗼𝘁𝗵𝗲𝗿𝗮𝗽𝗶𝗲𝘀

A new study in Immunity from Washington University School of Medicine in St. Louis reveals that #Tcells residing in tissues such as the #tonsils differ significantly from T cells circulating in the #blood. This challenges long-standing assumptions in #immunology and could transform how we assess immune responses to #vaccines, #infections, and #immunotherapies.

In one of the largest single-cell datasets of human T cells ever generated, researchers analyzed 5.7 million T cells from paired tonsil tissue and blood samples of 10 donors. Led by Dr. Naresha Saligrama, the team found profound differences in T cell subtypes and functions between compartments even within the same individual.

Why does this matter?

▪️ Less than 2% of the body’s T cells are actually in the blood, yet blood is currently the standard sample type used for immune monitoring.
▪️Many specialized T cells - including resident memory T cells and T follicular helper cells - exist almost exclusively in tissues, not blood.
▪️Tissue location can shape a T cell’s phenotype and its ability to recognize specific antigens.

🔍 Significance

This study highlights the need for a more tissue-aware approach to evaluating immune responses. Relying solely on blood samples may overlook critical populations of T cells that drive protection, disease progression, or therapeutic responses. Future vaccine design, #immunotherapy evaluation, and clinical diagnostics may need to incorporate location-specific immune profiling to truly understand human #immunity.

🗃️ See comments section for reference.

A toxin-secreting gut bacterium may fuel ulcerative colitis by killing protective immune cells that maintain intestinal homeostasis, according to a new study in Science.

The findings suggest potential for new treatment strategies.

📄: https://scim.ag/4oXOowT
#SciencePerspective: https://scim.ag/4a69oN6

The appendix is a small, worm-like diverticulum of the caecum, potentially having a role in regulating intestinal microbiota and immunology. Inflammation of the appendix, acute appendicitis, is one of the most common reasons for acute abdominal pain in children and adults and surgical emergency visits worldwide. The pathophysiology of appendicitis is still poorly understood. During the past decade, evidence has overturned the long-lasting dogma that all appendicitis cases have a clinical course inevitably progressing to perforation and life-threatening peritonitis unless operated upon in a timely manner. Instead, this natural course occurs only in a smaller proportion of patients, for whom emergency appendectomy remains mandatory. Advances in diagnostic accuracy following utilization of clinical scoring systems and imaging has enabled more accurate pre-interventional assessment of appendicitis disease severity. While some patients still require urgent surgery, the majority can be treated successfully with antibiotics, and in some the disease has even been shown to resolve spontaneously. This has confirmed the notion of at least two different forms of appendicitis: non-perforating and perforating, often referred to as uncomplicated and complicated appendicitis. Unified definitions of these forms are still undergoing rigorous research and debate, hampering both comparison of different studies and the establishment of unified treatment guidelines. The current knowledge on the safe and effective outcomes of non-operative treatment alternatives has further underlined the need for standardized uniform definitions of appendicitis severity and assessment of the success of two fundamentally different treatment options. Inflammation of the appendix, acute appendicitis, is one of the most common reasons for acute abdominal pain in children and adults and surgical emergency visits worldwide. In this Primer, Salminen and colleagues review the epidemiology, pathophysiology, diagnosis and management of appendicitis, and discuss future research areas.

Advances and prospects of respiratory mucosal vaccines: mechanisms, technologies, and clinical applications - npj Vaccines

https://lnkd.in/drB_Y9mh