Influenza A infection enhances antigen‐induced airway inflammation and hyperresponsiveness in young but not aged mice

Birmingham, Janette; Gillespie, Virginia; Li, Xiumin; Busse, Paula J.

doi:10.1111/cea.12365

Cited by 13 publications

(8 citation statements)

References 38 publications

(47 reference statements)

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“…This resembles changes seen in a severe asthma phenotype noted in some younger adults (60). Aged mouse models of asthma have demonstrated increased expression of airway IL-8 and cytokines associated with Th17 cells (61,62). This could contribute to increased airway neutrophilia.…”

Section: Update On the Effects Of Aging On Immune Function And Airwaymentioning

confidence: 55%

An Official American Thoracic Society Workshop Report: Evaluation and Management of Asthma in the Elderly

et al. 2016

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Asthma in the elderly (>65 yr old) is common and associated with higher morbidity and mortality than asthma in younger patients. The poor outcomes in this group are due, in part, to underdiagnosis and undertreatment. There are a variety of factors related to aging itself that affect the presentation of asthma in the elderly and influence diagnosis and management. Structural changes in the aging lung superimposed on structural changes due to asthma itself can worsen the disease and physiologic function. Changes in the aging immune system influence the cellular composition and function in asthmatic airways. These processes and differences from younger individuals with asthma are not well understood. Phenotypes of asthma in the elderly have not been clearly delineated, but it is likely that age of onset and overlap with chronic obstructive pulmonary disease impact disease characteristics. Physiologic tests and biomarkers used to diagnose and follow asthma in the elderly are generally similar to testing in younger individuals; however, whether they should be modified in aging has not been established. Confounding influences, such as comorbidities (increasing the risk of polypharmacy), impaired cognition and motor skills, psychosocial effects of aging, and age-related adverse effects of medications, impact both diagnosis and treatment of asthma in the elderly. Future efforts to understand asthma in the elderly must include geriatric-specific methodology to diagnose, characterize, monitor, and treat their disease.

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Section: Update On the Effects Of Aging On Immune Function And Airwaymentioning

confidence: 55%

An Official American Thoracic Society Workshop Report: Evaluation and Management of Asthma in the Elderly

et al. 2016

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“…Indeed, multiple mechanisms of IAV-associated regulation of subsequent antibacterial immune responses have been described [13]. In a broader context, it is conceivable that such regulation also affects non-infectious inflammatory conditions such as AAI and previous studies in different mouse models have indeed described significant effects of IAV infection [25][26][27]40,46,47]. In line with the heterogeneous IAV mediated effects described and discussed above, also the consequences for subsequent AAI are heterogeneous and include enhanced sensitization [25,26], aggravated allergic inflammation [27,46] and suppression of AAI [40,47].…”

Section: Discussionmentioning

confidence: 99%

“…In a broader context, it is conceivable that such regulation also affects non-infectious inflammatory conditions such as AAI and previous studies in different mouse models have indeed described significant effects of IAV infection [25][26][27]40,46,47]. In line with the heterogeneous IAV mediated effects described and discussed above, also the consequences for subsequent AAI are heterogeneous and include enhanced sensitization [25,26], aggravated allergic inflammation [27,46] and suppression of AAI [40,47]. Clinical data are mainly restricted to altered anti-IAV responses in asthmatics and IAV mediated acute exacerbations of existing allergic asthma, while the role of influenza viruses in asthma-development is mostly unclear [48][49][50].…”

Section: Discussionmentioning

confidence: 99%

Resolved Influenza A Virus Infection Has Extended Effects on Lung Homeostasis and Attenuates Allergic Airway Inflammation in a Mouse Model

Jorde

Kershaw

et al. 2020

Microorganisms

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Allergic airway inflammation (AAI) involves T helper cell type 2 (Th2) and pro-inflammatory responses to aeroallergens and many predisposing factors remain elusive. Influenza A virus (IAV) is a major human pathogen that causes acute respiratory infections and induces specific immune responses essential for viral clearance and resolution of the infection. Beyond acute infection, IAV has been shown to persistently affect lung homeostasis and respiratory immunity. Here we asked how resolved IAV infection affects subsequently induced AAI. Mice infected with a sublethal dose of IAV were sensitized and challenged in an ovalbumin mediated mouse model for AAI after resolution of the acute viral infection. Histological changes, respiratory leukocytes, cytokines and airway hyperreactivity were analyzed in resolved IAV infection alone and in AAI with and without previous IAV infection. More than five weeks after infection, we detected persistent pneumonia with increased activated CD4+ and CD8+ lymphocytes as well as dendritic cells and MHCII expressing macrophages in the lung. Resolved IAV infection significantly affected subsequently induced AAI on different levels including morphological changes, respiratory leukocytes and lymphocytes as well as the pro-inflammatory cytokine responses, which was clearly diminished. We conclude that IAV has exceptional persisting effects on respiratory immunity with substantial consequences for subsequently induced AAI.

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“…Neutrophil migration into the lung was also shown to be impaired in aged mice and rats (e.g. aged 18–24 months) following infectious challenges such as Francisella tularenesis , Pseudomonas aeruginosa, influenza A (Mares, et al 2010; Wen, et al 2014; Chen, et al 2014; Birmingham, et al 2014). This impairment might be attributed to a delay in the kinetics of neutrophil responses.…”

Section: Discussionmentioning

confidence: 99%

Age Impacts Pulmonary Inflammation and Systemic Bone Response to Inhaled Organic Dust Exposure

Poole

Romberger

Wyatt

et al. 2015

Journal of Toxicology and Environmental Health, Part A

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Agricultural workers have high rates of airway and skeletal health disease. Studies recently demonstrated that inhaled agricultural organic dust extract (ODE) induced-airway injury is associated with bone deterioration in an animal model. However, the effect of age in governing these responses to organic dusts is unclear, but might be important in future approaches. Young (7–9 weeks) and older (12–14 months) male C57BL/6 mice received intranasal (i.n.) inhalation exposure to ODE from swine confinement facilities once or daily for 3 weeks. Acute ODE-induced neutrophil influx and cytokine and chemokine (TNF-α, IL-6, CXCL1, CXCL2) airway production was reduced in older compared to young mice. Repetitive ODE treatment, however, increased lymphocyte recruitment and alveolar compartment histopathologic inflammatory changes in older mice. Whole lung cell infiltrate analysis revealed that young, but not older mice, repetitively treated with ODE demonstrated an elevated CD4:CD8 lymphocyte response. Acute inhalant ODE exposure resulted in a 4-fold and 1.5-fold rise in blood neutrophils in young and older mice, respectively. Serum IL-6 and CXCL1 levels were elevated in young and older mice i.n. exposed once to ODE, with increased CXCL1 levels in younger compared to older mice. Although older mice displayed reduced bone measurements compared to younger mice, younger rodents demonstrated ODE-induced decrease in bone mineral density, bone volume and bone micro-architecture quality as determined by CT analysis. Collectively, age impacts the airway injury, and systemic inflammatory and bone loss response to inhalant ODE, suggesting an altered and enhanced immunologic response in younger as compared to older counterparts.

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Influenza A infection enhances antigen‐induced airway inflammation and hyperresponsiveness in young but not aged mice

Cited by 13 publications

References 38 publications

An Official American Thoracic Society Workshop Report: Evaluation and Management of Asthma in the Elderly

An Official American Thoracic Society Workshop Report: Evaluation and Management of Asthma in the Elderly

Resolved Influenza A Virus Infection Has Extended Effects on Lung Homeostasis and Attenuates Allergic Airway Inflammation in a Mouse Model

Age Impacts Pulmonary Inflammation and Systemic Bone Response to Inhaled Organic Dust Exposure

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