scholarly journals Absence of β6 Integrin Reduces Influenza Disease Severity in Highly Susceptible Obese Mice

2018 ◽  
Vol 93 (2) ◽  
Author(s):  
Victoria Meliopoulos ◽  
Brandi Livingston ◽  
Lee-Ann Van de Velde ◽  
Rebekah Honce ◽  
Stacey Schultz-Cherry
Keyword(s):  
Influenza Virus ◽  
High Risk ◽  
Virus Infection ◽  
Disease Severity ◽  
Influenza Virus Infection ◽  
Obese Mouse ◽  
Type I ◽  
Type I Ifn ◽  
Obese Mice ◽  
Viral Spread

ABSTRACT Obese individuals are considered a high-risk group for developing severe influenza virus infection. While the exact mechanisms for increased disease severity remain under investigation, obese-mouse models suggest that increased acute lung injury (ALI), potentially due to enhanced viral spread and decreased wound repair, is likely involved. We previously demonstrated that upregulation of the lung epithelial cell β6 integrin during influenza virus infection was involved in disease severity. Knocking out β6 (β6 KO) resulted in improved survival. Of interest, obese mice have increased lung β6 integrin levels at homeostasis. Thus, we hypothesized that the protective effect seen in β6 KO mice would extend to the highly susceptible obese-mouse model. In the current study, we show that crossing β6 KO mice with genetically obese (ob/ob) mice (OBKO) resulted in reduced ALI and impaired viral spread, like their lean counterparts. Mechanistically, OBKO alveolar macrophages and epithelial cells had increased type I interferon (IFN) signaling, potentially through upregulated type I IFN receptor expression, which was important for the enhanced protection during infection. Taken together, our results indicate that the absence of an epithelial integrin can beneficially alter the pulmonary microenvironment by increasing protective type I IFN responses even in a highly susceptible obese-mouse model. These studies increase our understanding of influenza virus pathogenesis in high-risk populations and may lead to the development of novel therapies. IMPORTANCE Obesity is a risk factor for developing severe influenza virus infection. However, the reasons for this are unknown. We found that the lungs of obese mice have increased expression of the epithelial integrin β6, a host factor associated with increased disease severity. Knocking out integrin β6 in obese mice favorably altered the pulmonary environment by increasing type I IFN signaling, resulting in decreased viral spread, reduced lung injury, and increased survival. This study furthers our understanding of influenza virus pathogenesis in the high-risk obese population and may potentially lead to the development of novel therapies for influenza virus infection.

scholarly journals Type I IFN Receptor Signals Directly Stimulate Local B Cells Early following Influenza Virus Infection

2006 ◽  
Vol 176 (7) ◽  
pp. 4343-4351 ◽  
Author(s):  
Elizabeth S. Coro ◽  
W. L. William Chang ◽  
Nicole Baumgarth
Keyword(s):  
Influenza Virus ◽  
B Cells ◽  
Virus Infection ◽  
Influenza Virus Infection ◽  
Type I ◽  
Type I Ifn

scholarly journals Immunopathogenesis of SARS-CoV-2-induced pneumonia: lessons from influenza virus infection

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Masaaki Miyazawa
Keyword(s):  
Influenza Virus ◽  
T Cell ◽  
Virus Infection ◽  
Tissue Injury ◽  
Influenza Virus Infection ◽  
T Cell Responses ◽  
Type I ◽  
Upper Respiratory Tract ◽  
Viral Spread ◽  
Cell Responses

Abstract Factors determining the progression of frequently mild or asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection into life-threatening pneumonia remain poorly understood. Viral and host factors involved in the development of diffuse alveolar damage have been extensively studied in influenza virus infection. Influenza is a self-limited upper respiratory tract infection that causes acute and severe systemic symptoms and its spread to the lungs is limited by CD4+ T-cell responses. A vicious cycle of CCL2- and CXCL2-mediated inflammatory monocyte and neutrophil infiltration and activation and resultant massive production of effector molecules including tumor necrosis factor (TNF)-α, nitric oxide, and TNF-related apoptosis-inducing ligand are involved in the pathogenesis of progressive tissue injury. SARS-CoV-2 directly infects alveolar epithelial cells and macrophages and induces foci of pulmonary lesions even in asymptomatic individuals. Mechanisms of tissue injury in SARS-CoV-2-induced pneumonia share some aspects with influenza virus infection, but IL-1β seems to play more important roles along with CCL2 and impaired type I interferon signaling might be associated with delayed virus clearance and disease severity. Further, data indicate that preexisting memory CD8+ T cells may play important roles in limiting viral spread in the lungs and prevent progression from mild to severe or critical pneumonia. However, it is also possible that T-cell responses are involved in alveolar interstitial inflammation and perhaps endothelial cell injury, the latter of which is characteristic of SARS-CoV-2-induced pathology.

scholarly journals Type I IFN signaling facilitates the development of IL-10-producing effector CD8+T cells during murine influenza virus infection

2016 ◽  
Vol 46 (12) ◽  
pp. 2778-2788 ◽  
Author(s):  
Li Jiang ◽  
Shuyu Yao ◽  
Su Huang ◽  
Jeffrey Wright ◽  
Thomas J. Braciale ◽  
...  
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
Virus Infection ◽  
Cd8 T Cells ◽  
Influenza Virus Infection ◽  
Type I ◽  
Type I Ifn

scholarly journals Rapid Differentiation of Monocytes into Type I IFN-Producing Myeloid Dendritic Cells as an Antiviral Strategy against Influenza Virus Infection

2012 ◽  
Vol 189 (5) ◽  
pp. 2257-2265 ◽  
Author(s):  
Weiping Cao ◽  
Andrew K. Taylor ◽  
Renata E. Biber ◽  
William G. Davis ◽  
Jin Hyang Kim ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Influenza Virus ◽  
Virus Infection ◽  
Influenza Virus Infection ◽  
Type I ◽  
Type I Ifn ◽  
Myeloid Dendritic Cells

Impact of influenza virus during pregnancy: from disease severity to vaccine efficacy

2020 ◽  
Vol 15 (7) ◽  
pp. 441-453
Author(s):  
Ana Vazquez-Pagan ◽  
Rebekah Honce ◽  
Stacey Schultz-Cherry
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Immune Responses ◽  
Pregnant Women ◽  
Disease Severity ◽  
Influenza A ◽  
Antiviral Treatment ◽  
Influenza Virus Infection ◽  
Severe Influenza ◽  
The Impact

Pregnant women are among the individuals at the highest risk for severe influenza virus infection. Infection of the mother during pregnancy increases the probability of adverse fetal outcomes such as small for gestational age, preterm birth and fetal death. Animal models of syngeneic and allogeneic mating can recapitulate the increased disease severity observed in pregnant women and are used to define the mechanism(s) of that increased severity. This review focuses on influenza A virus pathogenesis, the unique immunological landscape during pregnancy, the impact of maternal influenza virus infection on the fetus and the immune responses at the maternal–fetal interface. Finally, we summarize the importance of immunization and antiviral treatment in this population and highlight issues that warrant further investigation.

Obesity worsens the outcome of influenza virus infection associated with impaired type I interferon induction in mice

2019 ◽  
Vol 513 (2) ◽  
pp. 405-411 ◽  
Author(s):  
Ho Namkoong ◽  
Makoto Ishii ◽  
Hideki Fujii ◽  
Takahiro Asami ◽  
Kazuma Yagi ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Type I Interferon ◽  
Influenza Virus Infection ◽  
Type I ◽  
Interferon Induction

scholarly journals 1H NMR-Based Profiling Reveals Differential Immune-Metabolic Networks during Influenza Virus Infection in Obese Mice

PLoS ONE ◽  
2014 ◽  
Vol 9 (5) ◽  
pp. e97238 ◽  
Author(s):  
J. Justin Milner ◽  
Jue Wang ◽  
Patricia A. Sheridan ◽  
Tim Ebbels ◽  
Melinda A. Beck ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
1H Nmr ◽  
Metabolic Networks ◽  
Influenza Virus Infection ◽  
Obese Mice

scholarly journals A Perfect Storm: Increased Colonization and Failure of Vaccination Leads to Severe Secondary Bacterial Infection in Influenza Virus-Infected Obese Mice

mBio ◽  
2017 ◽  
Vol 8 (5) ◽  
Author(s):  
Erik A. Karlsson ◽  
Victoria A. Meliopoulos ◽  
Nicholas C. van de Velde ◽  
Lee-Ann van de Velde ◽  
Beth Mann ◽  
...  
Keyword(s):  
Public Health ◽  
Influenza Virus ◽  
Virus Infection ◽  
Bacterial Infection ◽  
Antibiotic Treatment ◽  
Influenza Virus Infection ◽  
Health Concern ◽  
Obese Mice ◽  
Secondary Bacterial Infection ◽  
Perfect Storm

ABSTRACT Obesity is a risk factor for developing severe disease following influenza virus infection; however, the comorbidity of obesity and secondary bacterial infection, a serious complication of influenza virus infections, is unknown. To fill this gap in knowledge, lean and obese C57BL/6 mice were infected with a nonlethal dose of influenza virus followed by a nonlethal dose of Streptococcus pneumoniae. Strikingly, not only did significantly enhanced death occur in obese coinfected mice compared to lean controls, but also high mortality was seen irrespective of influenza virus strain, bacterial strain, or timing of coinfection. This result was unexpected, given that most influenza virus strains, especially seasonal human A and B viruses, are nonlethal in this model. Both viral and bacterial titers were increased in the upper respiratory tract and lungs of obese animals as early as days 1 and 2 post-bacterial infection, leading to a significant decrease in lung function. This increased bacterial load correlated with extensive cellular damage and upregulation of platelet-activating factor receptor, a host receptor central to pneumococcal invasion. Importantly, while vaccination of obese mice against either influenza virus or pneumococcus failed to confer protection, antibiotic treatment was able to resolve secondary bacterial infection-associated mortality. Overall, secondary bacterial pneumonia could be a widespread, unaddressed public health problem in an increasingly obese population. IMPORTANCE Worldwide obesity rates have continued to increase. Obesity is associated with increased severity of influenza virus infection; however, very little is known about respiratory coinfections in this expanding, high-risk population. Our studies utilized a coinfection model to show that obesity increases mortality from secondary bacterial infection following influenza virus challenge through a “perfect storm” of host factors that lead to excessive viral and bacterial outgrowth. In addition, we found that vaccination of obese mice against either virus or bacteria failed to confer protection against coinfection, but antibiotic treatment did alleviate mortality. Combined, these results represent an understudied and imminent public health concern in a weighty portion of the global population. IMPORTANCE Worldwide obesity rates have continued to increase. Obesity is associated with increased severity of influenza virus infection; however, very little is known about respiratory coinfections in this expanding, high-risk population. Our studies utilized a coinfection model to show that obesity increases mortality from secondary bacterial infection following influenza virus challenge through a “perfect storm” of host factors that lead to excessive viral and bacterial outgrowth. In addition, we found that vaccination of obese mice against either virus or bacteria failed to confer protection against coinfection, but antibiotic treatment did alleviate mortality. Combined, these results represent an understudied and imminent public health concern in a weighty portion of the global population.

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