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Microbes & Immunity Pulmonary immunity: Pathogens versus protectors

biomarkers that influence the progression of respiratory and microbiome transplantation – are being developed
diseases such as influenza, tuberculosis, or COVID-19. For to restore microbial balance and enhance pulmonary
example, simulations have highlighted the critical role of immunity. Advances in metagenomic sequencing and
IFN responses in controlling viral replication, as well as machine learning are enabling researchers to explore the
the detrimental effects of excessive inflammation in severe complex interactions between microbial communities
pneumonia cases. One of the most promising applications and immune cells, creating opportunities for personalized
of these computational simulations is accelerating novel interventions. In pulmonary immune responses, the
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therapeutic development. By virtually screening thousands microbiome acts as both foe and ally. Understanding its
of drug candidates and their effects on immune–pathogen influence is crucial for the development of novel therapeutic
interactions, researchers can prioritize the most effective approaches that shift the balance toward protection, offering
interventions for experimental validation. This approach new hope to millions of individuals affected by respiratory
not only reduces the time and cost of traditional drug diseases. As research on the lung microbiome progresses,
discovery but also opens new avenues for personalized one thing remains clear: these microscopic inhabitants hold
medicine, enabling treatments tailored to an individual’s the key to shaping the future of pulmonary medicine.
unique immune profile. f. The balance between protection and pathology
e. Microbiome influence The pulmonary immune system must maintain a
Once considered sterile, the human lung is now delicate balance between eliminating pathogens and
recognized as a dynamic ecosystem rich in microbial life. preventing excessive inflammation. Disruption of this
The pulmonary microbiome – a complex community of balance can lead to chronic inflammatory diseases such
bacteria, viruses, fungi, and other microorganisms – plays as asthma, COPD, and pulmonary fibrosis. For instance,
a pivotal role in shaping immune responses within the an overactive Th2 response characterizes allergic asthma,
respiratory system. This dynamic interplay between the lung while excessive neutrophil activity is associated with
microbiome and the immune system can influence whether tissue damage in COPD. However, this delicate balance
these microorganisms act as harmful pathogens or beneficial between protection and pathology often acts as a double-
protectors in the ongoing pulmonary immune response. edged sword. While robust immune responses are
Recent research highlights the dual nature of the lung essential for eliminating harmful pathogens, excessive or
microbiome. A balanced and diverse microbial community dysregulated immunity can lead to tissue damage, chronic
contributes to immune homeostasis by training the inflammation, and pathological conditions such as fibrosis
immune system to distinguish between harmless invaders or autoimmune disorders. Understanding this balance is
and genuine threats. For example, commensal bacteria can critical for developing innovative therapeutic strategies
stimulate the production of anti-inflammatory cytokines that enhance protective immunity without shifting the
and promote the development of Treg cells, which help balance toward pathology.
suppress excessive immune responses and prevent g. Protective immunity: The first line of defense
chronic inflammation. This protective role is essential for The lungs are constantly exposed to environmental
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maintaining lung health and resilience against infections. pathogens, allergens, and pollutants, necessitating a rapid
Conversely, dysbiosis – an imbalance in the microbial and efficient immune response. Innate immune systems –
community – can shift the balance toward pathogenicity. such as alveolar macrophages, dendritic cells, and epithelial
When harmful microbes dominate, they disrupt the barriers – play a pivotal role in detecting and neutralizing
epithelial barrier, trigger hyperactive immune responses, threats. These cells recognize pathogen-associated
and exacerbate conditions such as asthma, COPD, and molecular patterns and damage-associated molecular
pulmonary fibrosis. Pathogens such as P. aeruginosa patterns through pattern recognition receptors, initiating a
and Streptococcus pneumoniae exploit these imbalances, cascade of pro-inflammatory signals. Neutrophils, natural
leading to persistent infections and chronic inflammation. killer cells, and AMPs further contribute to pathogen
Moreover, the interaction between the microbiome and clearance, while adaptive immunity – mediated by T and
viral infections, such as influenza or SARS-CoV-2, further B cells – provides long-lasting protection through memory
complicates the immune response, as dysbiosis may impair responses. 23
the lung’s ability to mount an effective antiviral defense. However, the effectiveness of these responses depends
Innovative perspectives are emerging to enhance on precise regulation. For instance, alveolar macrophages
the microbiome’s protective potential while minimizing exhibit a unique ability to switch between pro- and anti-
its pathogenic risks. Therapeutic strategies – such as inflammatory phenotypes, ensuring inflammation resolves
probiotic therapies, targeted antimicrobial treatments, once the threat is eliminated. Similarly, Treg cells play a

Volume 2 Issue 4 (2025) 32 doi: 10.36922/MI025100019