Mechanisms by which obesity predisposes to severe H1N1 infection 1.0

• Research type

  Research Study

• Full title

  Mechanisms by which obesity predisposes to severe influenza A infection

• IRAS ID

  109549

• Contact name

  Sebastian Johnston

• Contact email

  s.johnston@imperial.ac.uk

• Sponsor organisation

  Imperial College

• Research summary

  Lay Summary of Results:

  Obesity is a well-recognized risk factor for severe influenza infections but the mechanisms underlying susceptibility are poorly understood. Here, we identify that obese individuals have deficient pulmonary antiviral immune responses in bronchoalveolar lavage cells but not in bronchial epithelial cells or peripheral blood dendritic cells. We show that the obese human airway metabolome is perturbed with associated increases in the airway concentrations of the adipokine leptin which correlated negatively with the magnitude of ex vivo antiviral responses. Exogenous pulmonary leptin administration in mice directly impaired antiviral type I interferon responses in vivo and ex vivo in cultured airway macrophages. Obese individuals hospitalised with influenza showed dysregulated upper airway immune responses. These studies provide insight into mechanisms driving propensity to severe influenza infections in obesity and raise the potential for development of leptin manipulation or interferon administration as novel strategies for conferring protection from severe infections in obese higher risk individuals.
  https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fpubmed.ncbi.nlm.nih.gov%252F37857661%252F%2FNBTI%2FiBG-AQ%2FAQ%2F1ca069a2-78f9-4bef-98d7-cfaa9d6fcb21%2F1%2FIfjQDpzEC_&data=05%7C02%7Csurreyborders.rec%40hra.nhs.uk%7Cce2e61ce5ba54b843aab08ddd3270ce5%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638898886860452149%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=MrjRjAa4yYcBFZ40rIIYy6DIOXk5anU5ALREk%2Fj%2BfRc%3D&reserved=0

  Has the registry been updated to include summary results?: No
  If yes - please enter the URL to summary results:
  If no – why not?: It was not registered.
  Did you follow your dissemination plan submitted in the IRAS application form (Q A51)?: Yes
  If yes, describe or provide URLs to disseminated materials: https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fpubmed.ncbi.nlm.nih.gov%252F37857661%252F%2FNBTI%2FiBG-AQ%2FAQ%2F1ca069a2-78f9-4bef-98d7-cfaa9d6fcb21%2F1%2FIfjQDpzEC_&data=05%7C02%7Csurreyborders.rec%40hra.nhs.uk%7Cce2e61ce5ba54b843aab08ddd3270ce5%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638898886860466844%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=BujtIq2Z6tFC%2FiExXnsWiXNrPnPs860LYP%2BmwBZn2f4%3D&reserved=0
  If pending, date when dissemination is expected:
  If no, explain why you didn't follow it:
  Have participants been informed of the results of the study?: No
  If yes, describe and/or provide URLs to materials shared and how they were shared:
  If pending, date when feedback is expected:
  If no, explain why they haven't: Fellow moved abroad.
  Have you enabled sharing of study data with others?: Yes
  If yes, describe or provide URLs to how it has been shared: https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fpubmed.ncbi.nlm.nih.gov%252F37857661%252F%2FNBTI%2FiBG-AQ%2FAQ%2F1ca069a2-78f9-4bef-98d7-cfaa9d6fcb21%2F1%2FIfjQDpzEC_&data=05%7C02%7Csurreyborders.rec%40hra.nhs.uk%7Cce2e61ce5ba54b843aab08ddd3270ce5%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638898886860480769%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=sWIf3%2B0nHbYMBqb4K9Tn0UDKBz7D8qQ1GaDWllaheoQ%3D&reserved=0
  If no, explain why sharing hasn't been enabled:
  Have you enabled sharing of tissue samples and associated data with others?: No
  If yes, describe or provide a URL:
  If no, explain why: There were used up.
  Captcha: 03AFcWeA4cv-4ayvHBnhI61SGz0YjYQ7WmUPEby1ZxWc5xNtbB8GKTQI5FG-gyYrzvoBfvXJFYEzIEHqnRKZxGEe0lWE7f9uZH4KG1fK9vvwEgllSw0imiuoHh9l2TuYrB9vMHh89o8ciij5TXWNn0vW1pwzDLLumO1Mr63dM8gWTimj39TuhMAWrP6RyNhSH1lJzcmNKzSndat7oCqm1-tUKBySebOMk3FgZboj893KYe9ytYPCj6kwzVsf7EYkn902klgpePWry0dJlm-U0ZyMbuUnwwDGiIsiiV6oZfWOWLmVaJiYPxJr9pM64LPfB6xzumnd8JszYr9txQ3JhQGDojrZfDd4rIXmMkHYoisEjKWATWoZaT5bCgyeeipFCoxq5FwnhKAdIoY1UHoeJxgSB-4He7B3axHq4d4pAFHuUFd5lal-JeccZWh51kb1n7jiD7ABKnnZCKDppgW-Ocay-1Kus6e6mdXdcbZDqndu1rXMLIhpgs17diWUvwLKRm2kEW3ImvlPCQrAd9-ThPVRPlCyZV-vGg-7L4KgSDp47yvolHSv6esAm0yDSsU6y5C8uzeqJm7VSayOa9FvvUsBWlthnfX5IJT7_pl1YM8mgYqcnXhkrPXUCNw5DENzSPdZW-4_9qwRyHafkFa_kTPRsIRG0s9YutLJ2lJ157YV0isWwRqTfv0WnE91k6wtX5y_NqLdGl4nl_knccVLyK5p9kElQiaQ3YMMXbZZQrLYYZ0XHvR8AYbelpLpRvibigkQ-9NeAZ1cIp3-rck2wOHi6Yjt283R6vq6Tq0RsB-dfEDBwGn0XLOzdiGUIhrebUD8eDgHJ5msefNEuruWHvjTmX7AR2ET9NbigBfzfq_2Pj_rLF7lkXCJorCxqrdtQTMBcyWL6Pl2VPRnL_sscsNMDHidC8A0BdgW8BthRE1SGp43T-DjJ_nCT5dhWOFX6obS1gUa5DaSCIXHkyqKsNGYk2x4n7mRQAEk8WBbyvx032KpMXI7PayP1mdkAHxchjFG35EjWBqVa_DDzJuwPk7eEQb-L_TR9ZoB2fkNUZ0aS3X9GluxQKkYc

• REC name

  London - Surrey Borders Research Ethics Committee

• REC reference

  12/LO/1812

• Date of REC Opinion

  17 Dec 2012

• REC opinion

  Further Information Favourable Opinion