T‑cell activation has long been seen as a relatively late step in antiviral defense. While the innate immune system reacts immediately, CD8 T cells are part of the adaptive response and usually act only after several days, targeting infected cells.
Researchers at the Institute of Lung Health and Immunity (LHI, Helmholtz Munich) and the Research Center Borstel (Leibniz Lung Center) now show that these cells can respond much earlier. They react to viral components far sooner than expected.

Live Imaging Tracks CD8 T-Cell Mobilization

The discovery was made possible by high-resolution intravital microscopy. This technique - available at only a few sites worldwide - allows biological processes to be observed directly in living organisms, in real time.
The team tracked how immune cells behave in the first hours after contact with viral components and what happens in the lung. The focus was on the SARS‑CoV‑2 envelope (E) protein, a structural component of the viral shell.
Within four hours of exposure to this protein, CD8 T cells were activated. They migrated into the lung, remained there for an extended time, and formed local clusters.

Innate Signaling Triggers Rapid Activation

The mechanism behind this rapid response was unexpected. The activation of CD8 T cells did not follow the known pathways of adaptive immunity. Instead, the innate immune system detects the E protein via the receptor TLR2 and triggers signals that activate T cells within hours.

Such rapid activation is typical for innate immune cells but had not been described for T cells in this way. The study therefore identifies a new mechanism by which viral structural proteins can induce a fast, innate-like T‑cell response.

“High-resolution intravital microscopy allows us to directly observe immune cell behavior in the lung and better understand how pulmonary immune responses unfold,” says Markus Rehberg, group leader at LHI and researcher in the German Center for Lung Research (DZL). 

“Our results suggest that innate and adaptive immunity work hand in hand much earlier than previously thought,” adds Silke Meiners, head of the Immunology and Cell Biology group at the Research Center Borstel.

Outlook: What Does This Mean?

In short, viral proteins can shape immune responses in the lung at a very early stage. Here, the SARS‑CoV‑2 envelope protein activates CD8 T cells before the immune system has fully recognized the virus. This opens up several perspectives:

• monitoring immune responses at the earliest stage of infection
• assessing disease risk more precisely
• targeting the interaction between innate and adaptive immunity in therapy

Original Publication

Shaalan et al., 2026: SARS-CoV-2 (E)-protein induces rapid TLR2-mediated T cell activation in mouse lungs revealed by intravital lung microscopy. ERS Publications. DOI: 10.1183/13993003.01064-2025

Now, in a comprehensive mechanistic follow-up study, Önder Yildirim (Director of the Institute of Lung Health and Immunity, LHI and Institute of Experimental Pneumology, IEP, Klinikum LMU) together with Erika von Mutius (Director IAP, Helmholtz Munich) and Guilherme Dragunas, Markus Klotz, Sirui Chen (LHI, Helmholtz Munich), have uncovered the molecular mechanism behind this protection. Their findings reveal how beneficial environmental exposure reshapes the immune system at the epigenetic level, effectively “training” it to resist allergic inflammation. 

Training the Immune System Before It Overreacts

Using a well-established experimental model of allergic asthma, the researchers exposed human and mice immune cells to farm dust extract triggering an allergic reaction. Compared to untreated controls, farm dust exposed showed:

• Significantly reduced lung inflammation
• Less mucus production, a hallmark of asthma
• A strongly dampened inflammatory immune response in the lungs

At the center of this shift were immune cells called macrophages, that normally help activate allergic responses. Instead of promoting inflammation, farm dust reprogrammed these macrophages. The cells reduced production of CCL8, a chemokine that attracts inflammatory eosinophils, and downregulated MHC class II molecules, thereby limiting antigen presentation to T cells, a crucial step in launching allergic immune responses.

How Does Farm Dust Reprogram Immunity?

The secret lies in how farm dust reshapes immune cells in the lungs. Normally, allergic asthma is driven by cells that present allergens to the immune system, triggering a chain reaction that leads to inflammation and breathing problems. Farm dust seems to interrupt this process. It reprograms macrophages through activation of PPARγ signaling and increased HDAC activity, chromatin accessibility at key inflammatory genes, so they stop sending strong allergy signals. This happens through epigenetic changes, meaning the dust influences which genes are active without altering the DNA itself. 

Önder Yildirim explains: “Our work shows that not all environmental exposures are harmful. We are deciphering how beneficial environmental signals can protect human health and actively strengthen immune resilience. What we learn from asthma may reshape prevention strategies across chronic lung diseases, including COPD and lung fibrosis.”

What Comes Next? From Barns to Better Prevention

Asthma and allergies affect hundreds of millions of people worldwide and remain a major public health challenge. Current treatments focus largely on managing symptoms after the disease has already developed. This research points to a different future: prevention.

The next challenge is to identify the exact components in farm dust that drive these protective effects. Could specific microbial molecules be isolated? Could they be safely delivered as inhaled treatments, nasal sprays, or early-life interventions?

While no one is suggesting that all children need to grow up in barns, the long-term vision is clear: identify the beneficial environmental components that promote immune tolerance and translate them into preventive strategies.

As von Mutius adds: “If we understand how the environment builds immune strength, we can move from treating chronic disease to preventing it. The future of medicine may lie not only in targeting pathology, but in harnessing the biology of resilience.”

Read full publication here!

The adult lung fundamentally possesses the capacity for repair. Following injury or inflammation, specialized cells can change their function, adapt to new demands and contribute to tissue restoration. This process, known as cellular plasticity, enables damaged structures to be replaced and airway function to be partially restored. At the same time, misdirected or incomplete regeneration may contribute to the development of chronic diseases such as pulmonary fibrosis or COPD.

The authors describe how modern technologies - particularly single-cell analyses - have significantly improved our understanding of the cellular composition and dynamics of lung tissue in recent years. As a result, repair processes can now be studied in far greater detail than before. New findings show that different cell populations respond flexibly to injury, activating complex signaling networks that determine whether regeneration succeeds or progresses toward disease.

For translational research, this highlights an important objective: to promote regenerative processes in a targeted manner without triggering pathological tissue remodeling. A better understanding of the underlying mechanisms could open new therapeutic avenues in the long term, for example through the targeted activation of reparative cell programs or interventions in disease-promoting signaling pathways.

The work therefore underscores the growing importance of fundamental biological research for the development of future treatment strategies for chronic lung diseases. At the same time, it demonstrates how closely insights from basic research are linked to clinical questions and how they can contribute to improving patient care.

Original article in European Respiratory Review: Cellular plasticity and regenerative mechanisms in the lung

The goal? To pinpoint which specific cell types and molecular pathways kickstart inflammation after nano materials enter the lungs. To capture these very first cellular responses, the scientists analyzed mouse lungs just 12 hours after exposure.

Key Findings: Structure Matters More Than Chemistry

The results reveal that chemically similar but structurally different nano materials trigger distinct inflammatory pathways:

• Spherical Carbon Particles (CNP)

 These activate alveolar epithelial cells, which release pro-inflammatory signaling molecules (cytokines). This recruits neutrophils (a type of immune cell) without causing significant cell damage.

• Fibrous Nano-tubes (CNT)

In contrast, tubular carbon nano tubes damage both epithelial and immune cells, leading to the release of alarm signals like IL-1α and IL-33. This triggers a strong, sometimes chronic inflammatory response.

An additional surprise: Mesenchymal cells, particularly lipofibroblasts near alveolar Type II cells, play a central role in shaping the intensity and nature of the inflammatory reaction.

A New Tool for Safer Nano materials: Introducing ToxAtlas

To make these findings widely accessible, the team developed ToxAtlas - an interactive online platform that maps cell-type-specific gene expression patterns and signaling pathways for different nano materials. Researchers can now connect material properties with biological effects, accelerating the development of safer, animal-free testing methods.

This research not only deepens our understanding of nano material toxicity but also offers a powerful tool for safer nano material development, reducing reliance on animal testing. ToxAtlas could improve the way we assess and mitigate the risks of emerging nano materials in medicine, industry, and environmental safety.

International Collaboration & Publication

The study, "Toward a ToxAtlas of Carbon-Based Nano materials: Single-Cell RNA Sequencing Reveals Initiating Cell Circuits in Pulmonary Inflammation," was published in ACS Nano and involved researchers from Germany, Denmark, Switzerland, and the UK.

Original publication: https://pubmed.ncbi.nlm.nih.gov/41183169/

Voss C, Han L, Ansari M, Strunz M, Haefner V, Angelidis I, Mayr CH, Berthing T, Zhou Q, Guenther EM, Huzain O, Schmid O, Vogel U, Gote-Schniering J, Gaedcke S, Theis FJ, Schiller HB, Stoeger T. Toward a ToxAtlas of Carbon-Based Nanomaterials: Single-Cell RNA Sequencing Reveals Initiating Cell Circuits in Pulmonary Inflammation. ACS Nano. 2025 Nov 18;19(45):39139-39156. doi: 10.1021/acsnano.5c12054. Epub 2025 Nov 3. PMID: 41183169; PMCID: PMC12632174.

In medicine, insufficient blood flow to tissue is known as ischemia. To prevent cell death, blood flow must be restored as quickly as possible (a process called reperfusion). Unfortunately, reperfusion itself can also damage tissue through the formation of oxygen radicals. Each year, millions of people in Europe suffer the consequences of ischemia-reperfusion injury. This common complication after stroke, heart attack, or organ transplantation can lead to tissue damage, cell death, and inflammation. Currently, there is no effective treatment. The FERROPath consortium aims to change that by exploring new therapeutic strategies.

Ferroptosis as a Key Mechanism

During the first funding period, the research team identified ferroptosis-specific lipid signatures that arise when blood flow is restored after reduced perfusion. In particular, biomarkers were detected in the brain and blood of stroke patients and confirmed in patient samples – pointing to the central role of ferroptosis in the disease mechanism. This specific form of iron-dependent cell death is triggered by oxidative stress and can be detected early through measurable proteins, opening new avenues for diagnosis and therapy.

New Phase for Diagnosis and Prevention

In the second funding period, the consortium will assess the stability and reproducibility of the lipid signatures to develop a standardized diagnostic tool. This will help identify the optimal time window for novel ferroptosis inhibitors and enable more individualized treatment: a key step toward precise, personalized stroke therapy.

The team led by Prof. Marcus Conrad and Dr. Bettina Proneth at the Institute of Metabolism and Cell Death is focusing on validating lipid biomarker signatures in preclinical models and testing new ferroptosis inhibitors. Conrad explains: “Our goal is to understand precisely when and how ferroptosis occurs during blood flow disturbances. By reliably identifying these characteristic lipid patterns, we could detect early on when tissue is at risk and intervene therapeutically before irreversible damage occurs.”

Prof. Önder Yildirim and Dr. Aicha Jeridi from the Institute for Lung Health and Immunity see significant potential for clinical applications. Their subproject focuses on validating a ferroptosis-specific biomarker panel for ischemia-reperfusion-induced lung injury. Yildirim explains: “Following transplants or acute blood flow disturbances, the lungs often sustain severe tissue damage, and currently there is no effective therapy.” Jeridi adds: “By deepening our understanding of ferroptosis, we aim to identify new ways to detect lung damage early and prevent it effectively.”

Learn more about FERROPath
 

One Key Insight: COPD Starts Early

A key message from the meeting was that COPD begins early in life. Factors such as prematurity and early-life infections can have long-term effects on lung development and function. As Mareike Lehmann emphasized in her opening remarks: “We need to understand these early origins of disease to not only cure but prevent COPD”.

Several talks explored why some individuals can recover from early life injuries and how this “catch-up” process can be decoded at the molecular level. Participants agreed that there is a critical window of opportunity to understand and potentially harness this regenerative capacity for therapy. 

Towards Better Markers of Disease Activity 

Standard diagnostic metrics such as FEV1 and GOLD stages are not sufficient to fully capture disease activity and progression. Advances in molecular imaging and biomarker discovery are therefore key. Spatial molecular profiling and cell-specific targeting could help determine when and where to intervene.

Prof. Stijn Verleden (Belgium) presented imaging tools to track lung regeneration, while Prof. Daniel Weiss (US) discussed the potential of gene- and cell-based therapies to promote tissue repair. 

Breakout sessions focused on translational research tools, including human organoids, lung-on-chip systems incorporating immune cells, and AI-based platforms such as digital twins – all contributing to a deeper understanding of COPD mechanisms and potential treatments.

Patient Perspectives and Recognitions

Patient advocate Michael Drohan shared his personal experience, illustrating the complex nature of COPD and the possibilities for recovery through rehabilitation.

The seminar also recognized outstanding early-career researchers with poster awards:

• Dr. Maria Camila Melo Narvaez (LHI, Helmholtz Munich/Institute for Lung Research, Marburg University)
• Hanne Voet (University Antwerpen, visited with an ERS Fellowship of LHI, Helmholtz Munich)
• Ayu Hitami Syarif (Medical University Graz)

Collaboration as the Key to Progress 

The meeting concluded with a clear call for continued international collaboration through networks such as COPD-iNET. As Prof. Önder Yildirim, Director of the Institute of Lung Health and Immunity at Helmholtz Munich, summarized:

“Only together we can prevent and cure COPD. The two days here in Prague once again demonstrated how important this network is in addressing this serious disease.”

About COPD-iNET:

The international network, co-founded by Önder Yildirim, Mareike Lehmann, Thomas Conlon, Theo Kapellos, Roxana Wasnick (all LHI, Helmholtz Munich) and international colleagues, continues to foster collaboration across disciplines and countries. The network’s primary focus is the advancement of translational COPD research by discussing ongoing projects, cutting edge human in vitro models, state-of-the art systems biology approaches and clinical cohorts. 

Learn more: copd-inet.com

Learn more: 

About the Institute of Lung Health and Immunity at Helmholtz Munich.

To the Lung Information Service at Helmholtz Munich.

Worldwide, COPD is the third leading cause of death, with more than three million people affected in Germany alone. A major challenge in managing the disease is that lung damage often develops long before diagnosis. Early warning signs such as persistent coughing or shortness of breath are frequently overlooked or underestimated.

The World COPD Day 2025 aims to raise global awareness of the disease and emphasize the importance of early detection, as COPD is often diagnosed only when it has already progressed significantly.

Research at Helmholtz Munich

At Helmholtz Munich, researchers are working to transform the prevention, diagnosis, and treatment of COPD. Their goal is to uncover the biological mechanisms underlying the disease and to identify new therapeutic and diagnostic approaches that enable earlier and more effective intervention.

The research focuses on understanding the immunological foundations of COPD and exploring how nutrition, environmental exposures, and immune responses interact during the onset and progression of the disease. By integrating these insights, Helmholtz Munich scientists aim to develop personalized strategies to prevent or slow disease progression and ultimately improve quality of life for those affected.

Learn more about the COPD research of Helmholtz Munich and partners

The Lung Information Service is a health information portal provided by Helmholtz Munich in cooperation with the German Center for Lung Research (DZL). It offers up-to-date, neutral, and scientifically validated information on acute and chronic lung diseases.

Information on COPD from the Lungeninformationsdienst (in German only)

Airborne fine particles and nanoparticles are closely linked to respiratory and cardiovascular diseases. Researchers led by Prof. Markus Rehberg and Dr. Qiongliang Liu from the LHI at Helmholtz Munich have now shown that inhaled nanoparticles do not spread evenly through the lungs but accumulate in specific hotspots deep in the alveoli. At these sites, alveolar macrophages quickly migrate toward the particles, engulf them, and release chemical signals that recruit neutrophils, another type of immune cell, to the same location.

Macrophages Drive Inflammation

The researchers found that macrophage mobility and phagocytosis are essential for triggering inflammation. When macrophage movement was blocked – or when receptors needed for particle uptake were inhibited – neutrophil recruitment was almost completely prevented. Likewise, using “stealth” nanoparticles that evade recognition blunted the immune response.

These findings show that macrophages act as key conductors of the lung’s first immune reaction: without their movement or uptake of nanoparticles, inflammation does not begin.

A Rapid, Pre-Loaded Defense

Rather than activating new genes, macrophages rely on pre-stored inflammatory molecules such as TNF-alpha and CXCL chemokines. This enables an ultra-fast, localized response, much like deploying a pre-packed emergency kit. Inhibiting this release with the drug cromolyn blocked neutrophil recruitment.

A Localized and Efficient Response

Alveolar macrophages are not passive cleaners but active sentinels that sense and shape immune reactions in the lungs. Their mobility, phagocytic activity, and communication with epithelial cells determine where and when inflammation occurs. Because the reaction remains confined to nanoparticle deposition sites, it represents a highly targeted defense mechanism.

Implication for Health and Research

These insights reveal how air pollutants and engineered nanoparticles provoke lung inflammation. Understanding these processes could help develop strategies to modulate macrophage activity, reducing harmful inflammation while maintaining essential immune protection.

Original publication

Liu et al., 2025: Alveolar macrophages initiate the spatially targeted recruitment of neutrophils after nanoparticle inhalation. Science Advances. DOI: 10.1126/sciadv.adx8586