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Microbes & Immunity Pulmonary immunity: Pathogens versus protectors

crucial role in suppressing excessive immune activation 6. Pathogen evasion strategies: Evading the
and preventing collateral tissue damage. pulmonary immune defense
4. Pathology: When protection goes awry The respiratory system serves as the pathogen’s primary
target due to its constant exposure to the external
Despite these regulatory mechanisms, the pulmonary environment. To successfully establish infection,
immune system is not infallible. Dysregulation can occur pathogens have developed sophisticated strategies to
at multiple levels, leading to pathological outcomes. For evade the host’s immune defenses. This review explores
example, excessive neutrophil recruitment and activation the complex mechanisms employed by pathogens to evade
– while effective against bacteria – can release reactive the pulmonary immune system, highlighting the ongoing
oxygen species and proteases that damage lung tissue, battle between microbial invaders and host defenses.
contributing to conditions such as acute respiratory distress
syndrome or COPD. Similarly, an overactive Th2 response 6.1. Pathogen disguise and antigenic variation
to harmless allergens may trigger asthma, characterized
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by airway hyperresponsiveness and remodeling. Chronic Pathogens evade immune detection by altering their surface
antigens, a strategy known as antigenic variation. For instance,
infections caused by pathogens such as M. tuberculosis or influenza viruses frequently mutate their hemagglutinin
P. aeruginosa further disrupt this balance. These pathogens and neuraminidase proteins, thereby enabling them to
evade immune detection and persist in the lungs, driving avoid recognition by pre-existing antibodies. Similarly,
sustained inflammation and tissue destruction. In some M. tuberculosis modifies its cell wall composition to avoid
cases, the immune response itself becomes the primary detection by pattern recognition receptors such as Toll-like
driver of pathology, as seen in idiopathic pulmonary
fibrosis, where aberrant wound healing and fibroblast receptors. This molecular mimicry allows pathogens to
disguise themselves within the host environment, delaying
activation lead to progressive scarring and loss of lung immune recognition and response.
function.
6.2. Inhibition of immune signaling
5. Innovative perspectives: Restoring the
delicate balance of pulmonary immune The pulmonary immune system is a complex network
responses of cells, cytokines, and signaling pathways designed to
protect the lungs against invading pathogens. However,
Recent advances in immunology and biotechnology many pathogens have developed sophisticated strategies
provide new insights into restoring the delicate balance to evade or inhibit immune signaling, shifting the balance
between protection and pathology. Targeting specific in their favor. Conversely, excessive or dysregulated
immune pathways, such as cytokine signaling (e.g., immune signaling can lead to chronic inflammation
interleukin [IL]-1β, IL-6, tumor necrosis factor α), shows and tissue damage, highlighting the delicate interplay
promising potential in modulating excessive inflammation between protection and pathology. This section explores
without compromising host defense. For instance, biologics the mechanisms used by pathogens to inhibit immune
like anti-IL-5 therapies have transformed the treatment of signaling and the therapeutic potential of targeted immune
eosinophilic asthma by selectively suppressing harmful modulation in pulmonary diseases.
immune responses. Another innovative approach involves
utilizing the power of the microbiome. 6.2.1. Pathogen-mediated inhibition of immune
signaling
Once considered sterile, the lung microbiome is
now recognized as a key player in immune regulation. Pathogens – including bacteria, viruses, and fungi
Dysbiosis, or microbial imbalance, has been linked to – have developed diverse strategies to evade host
chronic lung diseases, suggesting that restoring microbial immune defenses. For instance, M. tuberculosis inhibits
diversity may help rebalance immune responses. Probiotics macrophage activation and antigen presentation through
and prebiotics are being explored as potential therapies to multiple mechanisms. It secretes proteins – such as protein
achieve this balance. Furthermore, advances in gene editing tyrosine phosphatase A and protein tyrosine phosphatase
technologies, such as CRISPR-Cas9, hold promising B – which dephosphorylate key host signaling molecules,
potential for correcting genetic defects that contribute to including those in the mitogen-activated protein kinase
immune dysregulation. Similarly, personalized medicine and nuclear factor kappa B pathways, thereby suppressing
approaches – guided by biomarkers and genetic profiling pro-inflammatory cytokine production.
– aim to tailor therapies to individual patients, minimizing Similarly, respiratory viruses such as influenza A and
side effects and maximizing efficacy. SARS-CoV-2 encode proteins that disrupt IFN signaling.

Volume 2 Issue 4 (2025) 33 doi: 10.36922/MI025100019