NDLI: Diet-induced obese mice exhibit altered heterologous immunity during a secondary 2009 pandemic H1N1 $infection^{}$

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Diet-induced obese mice exhibit altered heterologous immunity during a secondary 2009 pandemic H1N1 $infection^{}$

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Diet-induced obese mice exhibit altered heterologous immunity during a secondary 2009 pandemic H1N1 $infection^{}$

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Milner, J. Justin Sheridan, Patricia A. Karlsson, Erik A. Schultz-Cherry, Stacey Beck, Melinda A. Shi, Qing
Description	Country affiliation: United States Author Affiliation: Milner JJ ( Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.)
Abstract	During the 2009 pandemic H1N1 influenza A virus (pH1N1) outbreak, obese individuals were at greater risk for morbidity and mortality from pandemic infection. However, the mechanisms contributing to greater infection severity in obese individuals remain unclear. Although most individuals lacked pre-existing, neutralizing Ab protection to the novel pH1N1 virus, heterologous defenses conferred from exposure to circulating strains or vaccination have been shown to impart protection against pH1N1 infection in humans and mice. Because obese humans and mice have impaired memory T cell and Ab responses following influenza vaccination or infection, we investigated the impact of obesity on heterologous protection from pH1N1 infection using a mouse model of diet-induced obesity. Lean and obese mice were infected with influenza A/Puerto Rico/8/34 (PR8) and 5 wk later challenged with a lethal dose of heterologous pH1N1. Cross-neutralizing Ab protection was absent in this model, but obese mice exhibited a significantly lower level of nonneutralizing, cross-reactive pH1N1 nucleoprotein Abs following the primary PR8 infection. Further, obese mice had elevated viral titers, greater lung inflammation and lung damage, and more cytotoxic memory CD8(+) T cells in the lung airways. Although obese mice had more regulatory T cells (Tregs) in the lung airways than did lean controls during the pH1N1 challenge, Tregs isolated from obese mice were 40% less suppressive than Tregs isolated from lean mice. In sum, excessive inflammatory responses to pH1N1 infection, potentially owing to greater viral burden and impaired Treg function, may be a novel mechanism by which obesity contributes to greater pH1N1 severity.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1202429
Journal	The Journal of Immunology
Issue Number	5
Volume Number	191
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2013-09-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Obesity Complications Immunology Orthomyxoviridae Infections Animals Antibodies, Viral Blood Cross Reactions Disease Models, Animal Enzyme-linked Immunosorbent Assay Flow Cytometry Influenza A Virus, H1n1 Subtype Mice Mice, Inbred C57bl Mice, Obese Pandemics Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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