Daily Respiratory Research Analysis
Analyzed 173 papers and selected 3 impactful papers.
Summary
Analyzed 173 papers and selected 3 impactful articles.
Selected Articles
1. Gut-lung axis: a novel mechanism involving microbiota dysbiosis-coordinated PLA2-TRPV1 neuroimmune crosstalk in nanoplastic-induced asthma exacerbation.
In OVA-sensitized mice, 20 nm polystyrene nanoplastics activated pulmonary PLA2, increased eicosanoid metabolites, upregulated TRPV1, and triggered neuropeptide release, amplifying NF-κB–driven Th2 inflammation and airway hyperresponsiveness. Dysbiosis increased hexa-acylated LPS and reduced short-chain fatty acids, engaging intestinal TLR4/NF-κB to reinforce a PLA2–TRPV1 neuroimmune loop via the gut–lung axis.
Impact: Reveals a coherent, multi-system mechanism linking environmental nanoplastics to asthma exacerbation through a gut–lung axis, identifying actionable nodes (PLA2, TRPV1, TLR4/NF-κB). This advances pathophysiological understanding and informs prevention and therapeutic target exploration.
Clinical Implications: While preclinical, findings support minimizing nanoplastic exposure in susceptible asthmatics and motivate trials of PLA2/TRPV1 pathway inhibitors. Biomonitoring of dysbiosis and oxidative stress markers may help identify high-risk phenotypes.
Key Findings
- PS-NP exposure activated pulmonary PLA2, increased PGE2 and LTB4, upregulated TRPV1, and induced substance P/CGRP release, enhancing NF-κB–driven Th2 inflammation (↑IL-4/IL-5/IL-13, ↓IFN-γ) and AHR.
- Gut dysbiosis with increased Pseudomonadota/Actinomycetota/Verrucomicrobiota elevated hexa-acylated LPS, activating intestinal TLR4/NF-κB and promoting lung inflammation via the gut–lung axis.
- Dysbiosis reduced short-chain fatty acids and altered glycerophospholipid/amino acid metabolism, further augmenting PLA2 activity and establishing a PLA2–TRPV1 neuroimmune positive feedback loop.
- Histopathology (HE, PAS, Masson) confirmed airway remodeling and tissue injury consistent with exacerbated asthma.
Methodological Strengths
- Integrated in vivo assessments: AHR, histopathology, immunohistochemistry, cytokines, and serum immunoglobulins
- Systems-level profiling with lung metabolomics and gut microbiota analysis linking metabolism, immunity, and neuroinflammation
Limitations
- Preclinical mouse model without human validation; exposure levels and duration relative to real-world conditions are uncertain
- Causal roles of individual microbial taxa and pathway nodes (e.g., TRPV1, PLA2) require interventional confirmation
Future Directions: Human exposure cohorts linking nanoplastic burden, dysbiosis, and asthma outcomes; randomized or pharmacological studies targeting PLA2/TRPV1 or TLR4/NF-κB; environmental measurements to define clinically relevant exposure thresholds.
This study, based on an OVA-sensitized mouse model, systematically elucidates the molecular mechanisms through which 20 nm polystyrene nanoplastics (PS-NPs) exacerbate asthma. A series of assessments were conducted, including measurements of airway hyperresponsiveness (AHR), histopathological analysis of lung tissue using HE, PAS and Masson staining, immunohistochemical detection of phospholipase A2 (PLA2) and TRPV1 expression, quantification of serum immunoglobulins and tissue cytokines, as well as lung metabolomics and gut microbiota profiling. Exposure to PS-NPs activated PLA2 in lung tissue, leading to the accumulation of arachidonic acid metabolites such as prostaglandin E2 and leukotriene B4. This process increased TRPV1 channel expression and promoted the release of neuropeptides including substance P and calcitonin gene-related peptide. The resulting cascade activated the NF-κB signaling pathway, thereby enhancing Th2-type inflammatory responses characterized by elevated IL-4, IL-5 and IL-13, reduced IFN-γ, and increased oxidative stress markers such as 8-OHdG. PS-NPs also significantly altered the gut microbiota, increasing the abundance of Pseudomonadota, Actinomycetota and Verrucomicrobiota. Gram-negative bacteria released substantial amounts of hexa-acylated LPS, which activated the intestinal TLR4/NF-κB pathway and promoted pulmonary inflammation through the gut-lung axis. Furthermore, dysbiosis-induced reductions in short-chain fatty acid production and abnormalities in glycerophospholipid and amino acid metabolism further enhanced pulmonary PLA2 activity, forming a PLA2-TRPV1-neuroimmune positive feedback loop that aggravated airway hyperresponsiveness and lung tissue damage. Overall, this study suggests the central role of a metabolism-immune-neuroinflammatory network mediated by the gut-lung axis in asthma aggravated by PS-NPs, providing new insights into the respiratory toxicity of environmental nanoplastics.
2. Mycobacterium avium infection induced PD-L1 overexpression in macrophages: a potential involvement with immune escape.
Using bulk RNA-seq, immunoblotting, and immunostaining in murine and human NTM lesions, the authors show that Mycobacterium avium induces PD-L1 upregulation in macrophages with a pro-inflammatory signature. Elevated macrophage PD-L1 correlates with reduced T-cell infiltration and increased PD-1 expression, implicating checkpoint-mediated immune escape and nominating PD-L1 blockade as a potential adjunctive therapy for pulmonary NTM infection.
Impact: Reveals a mechanistic immune-evasion pathway in NTM that is actionable with existing immunotherapies. Bridges basic immunology to a difficult-to-treat pulmonary infection, informing biomarker development and therapeutic trials.
Clinical Implications: PD-L1 expression in NTM-infected lesions could serve as a biomarker to identify patients who might benefit from PD-1/PD-L1 inhibitors, potentially as adjuncts to antibiotics in refractory pulmonary NTM. This also cautions that immune checkpoint status may influence host-pathogen dynamics.
Key Findings
- Mycobacterium avium infection drives PD-L1 overexpression in macrophages with a pro-inflammatory phenotype (bulk RNA-seq and western blot).
- In murine and human NTM lesions, higher macrophage PD-L1 associates with decreased T-cell infiltration and increased PD-1 (T-cell exhaustion).
- Findings support checkpoint-mediated immune escape in NTM and suggest PD-L1 inhibition as a therapeutic strategy.
Methodological Strengths
- Multi-system validation across in vitro macrophage models, NTM-infected mice, and human tissues.
- Integrated transcriptomic and protein-level assays linking phenotype to checkpoint expression.
Limitations
- Preclinical, non-interventional design; no direct therapeutic testing of PD-1/PD-L1 blockade in NTM.
- Generalizability across NTM species and clinical phenotypes requires further study.
Future Directions: Evaluate PD-1/PD-L1 inhibitors (alone and with antibiotics) in NTM preclinical models and early-phase trials; define predictive biomarkers (PD-L1 IHC, T-cell exhaustion signatures) and safety profiles in chronic infection.
Non-tuberculous mycobacteria (NTM) infections are difficult to cure completely with current treatments, and no specific drugs are available. However, recent reports have indicated that immune checkpoint inhibitors may effectively treat pulmonary NTM infections. In this study, we investigated the expression of immune checkpoint molecules in macrophages, the host cells of NTM, and assessed their impact on the microenvironment of infected lesions. Bulk-RNA sequencing and western blot analyses revealed that macrophages infected with Mycobacterium avium, an NTM species, exhibited a pro-inflammatory phenotype and increased PD-L1 expression. Additionally, immunostaining of an NTM-infected mouse model and human tissues showed that increased PD-L1 expression in macrophages was associated with decreased T cell infiltration and increased T cell exhaustion (upregulated PD-1 expression) within infected lesions. These findings suggest that NTM infections evade cellular immunity by enhancing PD-L1 expression in macrophages. Therefore, PD-L1 inhibition may be a promising therapeutic strategy against NTM infections.
3. Two-year persistence of MERS-CoV-specific antibody and T cell responses after MVA-MERS-S vaccination in healthy adults.
In a phase 1b extension, 48 adults receiving a 3-dose MVA-MERS-S regimen maintained detectable MERS-CoV–specific antibodies and T cells for at least 24 months after the third dose. Antibody levels approximated post–second dose peaks and cross-neutralized spike mutants, underscoring durable and potentially broad protection.
Impact: Demonstrates long-term durability and breadth of MERS vaccine–induced immunity, informing booster strategies and pandemic preparedness for coronaviruses.
Clinical Implications: Supports consideration of booster dosing to sustain long-term protection; cross-neutralization suggests resilience against antigenic drift, informing vaccine update intervals and stockpiling decisions.
Key Findings
- MERS-CoV–specific antibody and T-cell responses persisted for ≥24 months post–third MVA-MERS-S dose in healthy adults (n=48).
- Antibody levels remained comparable to the post–second dose peak and cross-neutralized spike mutants.
- Findings support booster importance for durable immunity despite unknown correlates of protection.
Methodological Strengths
- Randomized, double-blind parent trial with standardized immunogenicity assays; prospective durability follow-up.
- Assessment of both humoral and cellular immunity with functional cross-neutralization testing.
Limitations
- Modest sample size from a single cohort site; no clinical efficacy endpoints or established correlates of protection.
- Generalizability to other demographics and comorbid populations requires further study.
Future Directions: Define immune correlates of protection, assess booster intervals, and evaluate durability across age/comorbidity strata; explore heterologous prime-boost strategies for broader coronavirus preparedness.
MVA-MERS-S, a vaccine candidate against Middle East respiratory syndrome (MERS), was recently evaluated in a randomized, placebo-controlled, double-blind phase 1b clinical trial to assess its safety, immunogenicity, and optimal dosing in healthy adults in Hamburg and Rotterdam. A three-dose regimen was safe and elicited robust spike-specific antibody responses. We extended this trial to assess the two-year durability of MERS-CoV-specific antibody and T cell responses in 48 study participants of the Hamburg cohort. Our findings show that immune responses remain detectable for at least 24 months after the third vaccination. Antibodies persisted at levels comparable to the peak response observed after the second vaccination and were able to cross-neutralize MERS-CoV spike mutants. Although the immune correlates of protection against MERS remain unknown, the observed durability of humoral and cellular immune responses supports the potential of MVA-MERS-S as a promising MERS vaccine candidate and highlights the importance of a booster dose in sustaining long-term immunity.