Browsing by Subject "Immune"

Now showing 1 - 4 of 4
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    Air Pollution Exposure and the Lung-Brain Axis: Implications for Alzheimer's Disease
    (2022-03) Greve, Hendrik Jacob; Oblak, Adrian; Block, Michelle; Nass, Richard; Landreth, Gary
    Alzheimer’s disease (AD) is a devastating neurodegenerative disease that is expected to affect approximately 6.2 million Americans. Despite its high prevalence, the mechanisms underlying AD remain poorly understood. In recent years, increasing reports indicate that exposure to urban air pollution is a risk factor for the development of AD. However, the mechanistic underpinnings of this association are not well studied. Rats exposed to diesel exhaust (DE) showed neuroinflammation and impaired expression of TREM2 and disease-associated microglia (DAM), a cell subtype hypothesized to play beneficial roles during neurodegeneration, markers. Microglia in the cortex of rats exposed to DE, also showed decreased association with the vasculature, providing a novel link between the microglia and the brain vasculature. Examining the functional role of TREM2 during DE exposures, Trem2-/- mice showed an altered pro-inflammatory profile in both the brain and lungs in response to DE particles as well as altered phagocytic oxidase related gene expression. Examining another prominent component of air pollution, ozone (O3), in a mouse model of AD, it was discovered that subchronic O3 exposure exacerbates amyloid pathology through impaired microglial-plaque association in 5xFAD mice. 5xFAD mice exposed to O3 also showed increased expression of pro-inflammatory cytokines, increased markers of dystrophic neurites, and decreased expression of key acetylcholinergic pathway components. Examining the peri-plaque microenvironment, it was discovered that O3 dysregulates key DAM proteins and amyloid processing proteins. In the lung, it was found that O3 exacerbated immune cell infiltration in 5xFAD mice compared to WT controls, suggesting that ongoing amyloid pathology regulates pulmonary immune response to air pollution. To examine how O3-induced pulmonary immune responses may be signaling to the CNS, we examined the serum of 5xFAD mice, where HMGB1, VEGF, and IL-9 were upregulated. Injection of rHMGB1 into mice showed similar gene changes to 5xFAD mice exposed to O3, along with impaired Trem2 expression. Using a peripheral myeloid specific knock-out model of HMGB1, we also show that HMGB1 regulates O3-induced Trem2 expression impairment. Taken together, these data support that air pollution exposure impairs TREM2, DAM cells, and the microglial plaque response through a bidirectional lung-brain axis to exacerbate AD-like pathology.
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    Analysis and interpretation of inflammatory fluid markers in Alzheimer's disease: a roadmap for standardization
    (Springer Nature, 2025-04-15) Bettcher, Brianne M.; de Oliveira, Fabricio Ferreira; Willette, Auriel A.; Michalowska, Malgorzata M.; Santos Machado, Luiza; Rajbanshi, Binita; Borelli, Wyllians V.; Gámez Tansey, Malú; Rocha, Andréia; Suryadevara, Vidyani; Hu, William T.; Neurology, School of Medicine
    Growing interest in the role of the immune response in Alzheimer's Disease and related dementias (ADRD) has led to widespread use of fluid inflammatory markers in research studies. To standardize the use and interpretation of inflammatory markers in AD research, we build upon prior guidelines to develop consensus statements and recommendations to advance application and interpretation of these markers. In this roadmap paper, we propose a glossary of terms related to the immune response in the context of biomarker discovery/validation, discuss current conceptualizations of inflammatory markers in research, and recommend best practices to address key knowledge gaps. We also provide consensus principles to summarize primary conceptual, methodological, and interpretative issues facing the field: (1) a single inflammatory marker is likely insufficient to describe an entire biological cascade, and multiple markers with similar or distinct functions should be simultaneously measured in a panel; (2) association studies in humans are insufficient to infer causal relationships or mechanisms; (3) neuroinflammation displays time-dependent and disease context-dependent patterns; (4) neuroinflammatory mechanisms should not be inferred based solely on blood inflammatory marker changes; and (5) standardized reporting of CSF inflammatory marker assay validation and performance will improve incorporation of inflammatory markers into the biological AD criteria.
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    Evolving concepts in how viruses impact asthma
    (Elsevier, 2020-05) Altman, Matthew C.; Beigelman, Avraham; Ciaccio, Christina; Gern, James E.; Heymann, Peter W.; Jackson, Daniel J.; Kennedy, Joshua L.; Kloepfer, Kirsten; Lemanske, Robert F., Jr.; McWilliams, Laurie M.; Muehling, Lyndsey; Nance, Christy; Stokes Peebles, R., Jr.; Pediatrics, School of Medicine
    Over the past decade, there have been substantial advances in our understanding about how viral infections regulate asthma. Important lessons have been learned from birth cohort studies examining viral infections and subsequent asthma and from understanding the relationships between host genetics and viral infections, the contributions of respiratory viral infections to patterns of immune development, the impact of environmental exposure on the severity of viral infections, and how the viral genome influences host immune responses to viral infections. Further, there has been major progress in our knowledge about how bacteria regulate host immune responses in asthma pathogenesis. In this article, we also examine the dynamics of bacterial colonization of the respiratory tract during viral upper respiratory tract infection, in addition to the relationship of the gut and respiratory microbiomes with respiratory viral infections. Finally, we focus on potential interventions that could decrease virus-induced wheezing and asthma. There are emerging therapeutic options to decrease the severity of wheezing exacerbations caused by respiratory viral infections. Primary prevention is a major goal, and a strategy toward this end is considered.
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    Large-scale genomic study reveals robust activation of the immune system following advanced Inner Engineering meditation retreat
    (National Academy of Science, 2021) Chandran, Vijayendran; Bermúdez, Mei-Ling; Koka, Mert; Chandran, Brindha; Pawale, Dhanashri; Vishnubhotla, Ramana; Alankar, Suresh; Maturi, Raj; Subramaniam, Balachundhar; Sadhasivam, Senthilkumar; Anesthesia, School of Medicine
    The positive impact of meditation on human well-being is well documented, yet its molecular mechanisms are incompletely understood. We applied a comprehensive systems biology approach starting with whole-blood gene expression profiling combined with multilevel bioinformatic analyses to characterize the coexpression, transcriptional, and protein-protein interaction networks to identify a meditation-specific core network after an advanced 8-d Inner Engineering retreat program. We found the response to oxidative stress, detoxification, and cell cycle regulation pathways were down-regulated after meditation. Strikingly, 220 genes directly associated with immune response, including 68 genes related to interferon signaling, were up-regulated, with no significant expression changes in the inflammatory genes. This robust meditation-specific immune response network is significantly dysregulated in multiple sclerosis and severe COVID-19 patients. The work provides a foundation for understanding the effect of meditation and suggests that meditation as a behavioral intervention can voluntarily and nonpharmacologically improve the immune response for treating various conditions associated with excessive or persistent inflammation with a dampened immune system profile.