Exposure to combustion derived particulate matter exacerbates influenza infection in neonatal mice by inhibiting IL22 production

Abstract Background Particulate matter (PM) containing environmentally persistent free radicals (EPFRs) are formed during various combustion processes, including the thermal remediation of hazardous wastes. Exposure to PM adversely affects respiratory health in infants and is associated with increased morbidity and mortality due to acute lower respiratory tract infections. We previously reported that early-life exposure to PM damages the lung epithelium and suppresses immune responses to influenza virus (Flu) infection, thereby enhancing Flu severity. Interleukin 22 (IL22) is important in resolving lung injury following Flu infection. In the current study, we determined the effects of PM exposure on pulmonary IL22 responses using our neonatal mouse model of Flu infection. Results Exposure to PM resulted in an immediate (0.5–1-day post-exposure; dpe) increase in IL22 expression in the lungs of C57BL/6 neonatal mice; however, this IL22 expression was not maintained and failed to increase with either continued exposure to PM or subsequent Flu infection of PM-exposed mice. This contrasts with increased IL22 expression in age-matched mice exposed to vehicle and Flu infected. Activation of the aryl hydrocarbon receptor (AhR), which mediates the induction and release of IL22 from immune cells, was also transiently increased with PM exposure. The microbiome plays a major role in maintaining epithelial integrity and immune responses by producing various metabolites that act as ligands for AhR. Exposure to PM induced lung microbiota dysbiosis and altered the levels of indole, a microbial metabolite. Treatment with recombinant IL22 or indole-3-carboxaldehyde (I3A) prevented PM associated lung injury. In addition, I3A treatment also protected against increased mortality in Flu-infected mice exposed to PMs. Conclusions Together, these data suggest that exposure to PMs results in failure to sustain IL22 levels and an inability to induce IL22 upon Flu infection. Insufficient levels of IL22 may be responsible for aberrant epithelial repair and immune responses, leading to increased Flu severity in areas of high PM.

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The Contribution of Geogenic Particulate Matter to Lung Disease in Indigenous Children

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16152636 ◽

2019 ◽

Vol 16 (15) ◽

pp. 2636 ◽

Cited By ~ 2

Author(s):

Carrington C. J. Shepherd ◽

Holly D. Clifford ◽

Francis Mitrou ◽

Shannon M. Melody ◽

Ellen J. Bennett ◽

...

Keyword(s):

Particulate Matter ◽

Health Outcomes ◽

Lung Disease ◽

Respiratory Health ◽

Population Based ◽

Arid Environments ◽

Remote Communities ◽

Indigenous Children ◽

Tract Infections

Indigenous children have much higher rates of ear and lung disease than non-Indigenous children, which may be related to exposure to high levels of geogenic (earth-derived) particulate matter (PM). The aim of this study was to assess the relationship between dust levels and health in Indigenous children in Western Australia (W.A.). Data were from a population-based sample of 1077 Indigenous children living in 66 remote communities of W.A. (>2,000,000 km2), with information on health outcomes derived from carer reports and hospitalisation records. Associations between dust levels and health outcomes were assessed by multivariate logistic regression in a multi-level framework. We assessed the effect of exposure to community sampled PM on epithelial cell (NuLi-1) responses to non-typeable Haemophilus influenzae (NTHi) in vitro. High dust levels were associated with increased odds of hospitalisation for upper (OR 1.77 95% CI [1.02–3.06]) and lower (OR 1.99 95% CI [1.08–3.68]) respiratory tract infections and ear disease (OR 3.06 95% CI [1.20–7.80]). Exposure to PM enhanced NTHi adhesion and invasion of epithelial cells and impaired IL-8 production. Exposure to geogenic PM may be contributing to the poor respiratory health of disadvantaged communities in arid environments where geogenic PM levels are high.

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Particulate matter in ambient air and its association with alterations in lung functions and respiratory health problems among outdoor exercisers in National Capital Region, India

Atmospheric Pollution Research ◽

10.5094/apr.2015.070 ◽

2015 ◽

Vol 6 (4) ◽

pp. 618-625 ◽

Cited By ~ 10

Author(s):

Chandrasekharan Nair Kesavachandran ◽

Ritul Kamal ◽

Vipin Bihari ◽

Manoj Kumar Pathak ◽

Amarnath Singh

Keyword(s):

Particulate Matter ◽

Respiratory Health ◽

Ambient Air ◽

Health Problems ◽

National Capital Region ◽

Capital Region ◽

Lung Functions ◽

National Capital

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Prospective evaluation of respiratory health benefits from reduced exposure to airborne particulate matter

International Journal of Environmental Health Research ◽

10.1080/09603123.2017.1292497 ◽

2017 ◽

Vol 27 (2) ◽

pp. 126-135 ◽

Cited By ~ 13

Author(s):

Yanhui Hao ◽

Guanghui Zhang ◽

Bin Han ◽

Xiaowen Xu ◽

Nannan Feng ◽

...

Keyword(s):

Particulate Matter ◽

Respiratory Health ◽

Health Benefits ◽

Airborne Particulate Matter ◽

Prospective Evaluation ◽

Airborne Particulate

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Particulate Matter Composition and Respiratory Health

Epidemiology ◽

10.1097/ede.0000000000000264 ◽

2015 ◽

Vol 26 (3) ◽

pp. 300-309 ◽

Cited By ~ 64

Author(s):

Ulrike Gehring ◽

Rob Beelen ◽

Marloes Eeftens ◽

Gerard Hoek ◽

Kees de Hoogh ◽

...

Keyword(s):

Particulate Matter ◽

Respiratory Health

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Sinomenine ameliorates septic acute lung injury in mice by modulating gut homeostasis via aryl hydrocarbon receptor/Nrf2 pathway

European Journal of Pharmacology ◽

10.1016/j.ejphar.2021.174581 ◽

2021 ◽

pp. 174581

Author(s):

Wei Song ◽

Xiaoting Yang ◽

Wanqiu Wang ◽

Zi Wang ◽

Jie Wu ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Aryl Hydrocarbon Receptor ◽

Nrf2 Pathway ◽

Aryl Hydrocarbon ◽

Gut Homeostasis

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Altered thymocyte and T cell development in neonatal mice with hyperoxia-induced lung injury

Journal of Perinatal Medicine ◽

10.1515/jpm-2016-0234 ◽

2018 ◽

Vol 46 (4) ◽

pp. 441-449

Author(s):

Sowmya Angusamy ◽

Tamer Mansour ◽

Mohammed Abdulmageed ◽

Rachel Han ◽

Brian C. Schutte ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Lung Injury ◽

T Cell Development ◽

Adaptive Immune System ◽

Cell Development ◽

Thymocyte Development ◽

Double Positive ◽

Neonatal Mice ◽

Single Positive

Abstract Background: The adaptive immune system of neonates is relatively underdeveloped. The thymus is an essential organ for adaptive T cell development and might be affected during the natural course of oxygen induced lung injury. The effect of prolonged hyperoxia on the thymus, thymocyte and T cell development, and its proliferation has not been studied extensively. Methods: Neonatal mice were exposed to 85% oxygen (hyperoxia) or room air (normoxia) up to 28 days. Flow cytometry using surface markers were used to assay for thymocyte development and proliferation. Results: Mice exposed to prolonged hyperoxia had evidence of lung injury associated alveolar simplification, a significantly lower mean weight, smaller thymic size, lower mean thymocyte count and higher percentage of apoptotic thymocytes. T cells subpopulation in the thymus showed a significant reduction in the count and proliferation of double positive and double negative T cells. There was a significant reduction in the count and proliferation of single positive CD4+ and CD8+ T cells. Conclusions: Prolonged hyperoxia in neonatal mice adversely affected thymic size, thymocyte count and altered the distribution of T cells sub-populations. These results are consistent with the hypothesis that prolonged hyperoxia causes defective development of T cells in the thymus.

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Respiratory tract infections and gut microbiome modifications: A systematic review

PLoS ONE ◽

10.1371/journal.pone.0262057 ◽

2022 ◽

Vol 17 (1) ◽

pp. e0262057

Author(s):

Claire A. Woodall ◽

Luke J. McGeoch ◽

Alastair D. Hay ◽

Ashley Hammond

Keyword(s):

Systematic Review ◽

Respiratory Tract ◽

Cohort Studies ◽

Gut Microbiome ◽

Respiratory Tract Infections ◽

Respiratory Health ◽

Meta Analysis ◽

Bacterial Pathogen ◽

Healthy Controls ◽

Tract Infections

Respiratory tract infections (RTIs) are extremely common and can cause gastrointestinal tract symptoms and changes to the gut microbiota, yet these effects are poorly understood. We conducted a systematic review to evaluate the reported evidence of gut microbiome alterations in patients with a RTI compared to healthy controls (PROSPERO: CRD42019138853). We systematically searched Medline, Embase, Web of Science, Cochrane and the Clinical Trial Database for studies published between January 2015 and June 2021. Studies were eligible for inclusion if they were human cohorts describing the gut microbiome in patients with an RTI compared to healthy controls and the infection was caused by a viral or bacterial pathogen. Dual data screening and extraction with narrative synthesis was performed. We identified 1,593 articles and assessed 11 full texts for inclusion. Included studies (some nested) reported gut microbiome changes in the context of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) (n = 5), influenza (H1N1 and H7N9) (n = 2), Tuberculosis (TB) (n = 4), Community-Acquired Pneumonia CAP (n = 2) and recurrent RTIs (rRTI) (n = 1) infections. We found studies of patients with an RTI compared to controls reported a decrease in gut microbiome diversity (Shannon) of 1.45 units (95% CI, 0.15–2.50 [p, <0.0001]) and a lower abundance of taxa (p, 0.0086). Meta-analysis of the Shannon value showed considerable heterogeneity between studies (I2, 94.42). Unbiased analysis displayed as a funnel plot revealed a depletion of Lachnospiraceae, Ruminococcaceae and Ruminococcus and enrichment of Enterococcus. There was an important absence in the lack of cohort studies reporting gut microbiome changes and high heterogeneity between studies may be explained by variations in microbiome methods and confounder effects. Further human cohort studies are needed to understand RTI-induced gut microbiome changes to better understand interplay between microbes and respiratory health.

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