Sexual dimorphism in lung function responses to acute influenza A infection

Larcombe, Alexander N.; Foong, Rachel E.; Bozanich, Elizabeth M.; Berry, Luke J.; Garratt, Luke W.; Gualano, Rosa C.; Jones, Juli E.; Dousha, Lovisa; Zosky, Graeme R.; Sly, Peter D.

doi:10.1111/j.1750-2659.2011.00236.x

Cited by 71 publications

(83 citation statements)

References 36 publications

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“…Compared with B6 females, both B6 (χ 2 = 8.2, df = 1, P = 0.004) and B6-like males (χ 2 = 11.2, df = 1, P = 0.0008) were significantly less susceptible to IAV infection, as expected; however, ST-like males were not significantly different from B6 females (χ 2 = 1.1, df = 1, P = 0.5). The sex difference seen between B6 and B6-like males vs. B6 females, whereby females display greater susceptibility to IAV, is consistent with the previously reported sex difference between B6 males and females (2,28), and our results suggest that this sex difference can be overridden by ChrY variants in the ST-like group. Taken together, these data establish that genetic variation in ChrY influences the survival of male mice following primary infection with IAV, and thus contributes to the associated sex differences.…”

Section: B6supporting

confidence: 92%

Genetic variation in chromosome Y regulates susceptibility to influenza A virus infection

Krementsov

Case

Dienz

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Males of many species, ranging from humans to insects, are more susceptible than females to parasitic, fungal, bacterial, and viral infections. One mechanism that has been proposed to account for this difference is the immunocompetence handicap model, which posits that the greater infectious disease burden in males is due to testosterone, which drives the development of secondary male sex characteristics at the expense of suppressing immunity. However, emerging data suggest that cell-intrinsic (chromosome X and Y) sex-specific factors also may contribute to the sex differences in infectious disease burden. Using a murine model of influenza A virus (IAV) infection and a panel of chromosome Y (ChrY) consomic strains on the C57BL/6J background, we present data showing that genetic variation in ChrY influences IAV pathogenesis in males. Specific ChrY variants increase susceptibility to IAV in males and augment pathogenic immune responses in the lung, including activation of proinflammatory IL-17–producing γδ T cells, without affecting viral replication. In addition, susceptibility to IAV segregates independent of copy number variation in multicopy ChrY gene families that influence susceptibility to other immunopathological phenotypes, including survival after infection with coxsackievirus B3. These results demonstrate a critical role for genetic variation in ChrY in regulating susceptibility to infectious disease.

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Section: B6supporting

confidence: 92%

Genetic variation in chromosome Y regulates susceptibility to influenza A virus infection

Krementsov

Case

Dienz

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…There is growing debate around whether the relationship between early respiratory infection, particularly viral infection, and later development of respiratory morbidity or asthma is causal [12]. Causation has been demonstrated in mouse models with long-term impairment of lung function following early influenza infection [30]. Our retrospective observational study cannot demonstrate causation, rather the association between the exposure and outcome, where in this case, exposure may be just early signs of the disease (or its exacerbations).…”

Section: Discussionmentioning

confidence: 82%

Infant respiratory infections and later respiratory hospitalisation in childhood

2015

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Acute respiratory infections (ARI) cause significant morbidity in infancy. We sought to quantify the relationship between ARI and development of respiratory morbidity in early childhood.Population-based longitudinal hospitalisation data were linked to perinatal, birth and death records for 145 580 Western Australian children from 1997 to 2002. We conducted Cox regression with sensitivity analyses to quantify the risk of recurrent ARI in infancy for respiratory hospitalisation after the age of 3 years.ARI in infancy was significantly related to respiratory hospitalisation before (hazard ratio (HR) 3.5, 95% CI 3.1-3.8) and after (HR 3.0, 95% CI 2.6-3.4) adjusting for known risk factors including maternal smoking during pregnancy, season of birth, delivery mode and gestational age. We noted a dose response with the number and length of infant ARI hospitalisations and increasing risk with no effect modification by gestational age. Results were similar when later respiratory hospitalisations were restricted to asthma hospitalisations only.Recurrent hospitalisations for ARI in infancy significantly increase the risk of respiratory morbidity and asthma requiring hospitalisation after the age of 3 years in a dose-response fashion. The increase in relative risk is not modified by gestational age. Efforts to reduce the occurrence of infant ARI are likely to have significant public health benefits. @ERSpublications Recurrent infant acute respiratory infections: the major predictor of later hospitalisation for respiratory morbidity http://ow.ly/NVmGv

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“…This may be due to the strain of influenza we used (Influenza A/Memphis/1/71) which causes significant impairments in lung function in mice 24 , 25 . In this study, DEP exposure did not alter lung function on its own, so any potential further impairments caused by it in conjunction with influenza infection would likely have been eclipsed by the significant physiological impairments due to influenza infection.…”

Section: Discussionmentioning

confidence: 71%

“…Three time points were used; 6, 24 hours or 7 days post‐DEP exposure. These time points were the equivalent of 4, 5 and 11 days post‐influenza inoculation and were chosen based on previous work assessing the peak and resolution of inflammation 25 , 39 . Mice were injected with ∼two thirds of the dose to induce a surgical level of anaesthesia.…”

Section: Methodsmentioning

confidence: 99%

Acute diesel exhaust particle exposure increases viral titre and inflammation associated with existing influenza infection, but does not exacerbate deficits in lung function

Larcombe

Foong

Boylen

et al. 2012

Influenza Resp Viruses

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Please cite this paper as: Larcombe et al. (2012) Acute diesel exhaust particle exposure increases viral titre and inflammation associated with existing influenza infection, but does not exacerbate deficits in lung function. Influenza and Other Respiratory Viruses DOI:10.1111/irv.12012. Background Exposure to diesel exhaust particles (DEP) is thought to exacerbate many pre‐existing respiratory diseases, including asthma, bronchitis and chronic obstructive pulmonary disease, however, there is a paucity of data on whether DEP exacerbates illness due to respiratory viral infection. Objectives To assess the physiological consequences of an acute DEP exposure during the peak of influenza‐induced illness. Methods We exposed adult female BALB/c mice to 100 μg DEP (or control) 3·75 days after infection with 104·5 plaque forming units of influenza A/Mem71 (or control). Six hours, 24 hours and 7 days after DEP exposure we measured thoracic gas volume and lung function at functional residual capacity. Bronchoalveolar lavage fluid was taken for analyses of cellular inflammation and cytokines, and whole lungs were taken for measurement of viral titre. Results Influenza infection resulted in significantly increased inflammation, cytokine influx and impairment to lung function. DEP exposure alone resulted in less inflammation and cytokine influx, and no impairment to lung function. Mice infected with influenza and exposed to DEP had higher viral titres and neutrophilia compared with infected mice, yet they did not have more impaired lung mechanics than mice infected with influenza alone. Conclusions A single dose of DEP is not sufficient to physiologically exacerbate pre‐existing respiratory disease caused by influenza infection in mice.

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Sexual dimorphism in lung function responses to acute influenza A infection

Cited by 71 publications

References 36 publications

Genetic variation in chromosome Y regulates susceptibility to influenza A virus infection

Genetic variation in chromosome Y regulates susceptibility to influenza A virus infection

Infant respiratory infections and later respiratory hospitalisation in childhood

Acute diesel exhaust particle exposure increases viral titre and inflammation associated with existing influenza infection, but does not exacerbate deficits in lung function

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