Exopolysaccharides from Lactobacillus delbrueckii ssp. bulgaricus OLL1073R‐1 prevent influenza virus infection and attenuate secondary bacterial infection risk

2022 ◽  
Author(s):  
Hiroki Ishikawa ◽  
Yoshihiro Kuno ◽  
Chikara Kohda ◽  
Hiraku Sasaki ◽  
Ryuichi Nagashima ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Bacterial Infection ◽  
Influenza Virus Infection ◽  
Infection Risk ◽  
Lactobacillus Delbrueckii ◽  
Secondary Bacterial Infection

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.

scholarly journals THE INFLUENCE OF INFLUENZA VIRUS INFECTION ON EXOGENOUS STAPHYLOCOCCAL AND ENDOGENOUS MURINE BACTERIAL INFECTION OF THE BRONCHOPULMONARY TISSUES OF MICE

1961 ◽  
Vol 114 (2) ◽  
pp. 237-256 ◽  
Author(s):  
Thomas F. Sellers ◽  
Jerome Schulman ◽  
Claude Bouvier ◽  
Robert McCune ◽  
Edwin D. Kilbourne
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Respiratory Tract ◽  
Bacterial Infection ◽  
Influenza A Virus ◽  
Influenza A ◽  
Defense Mechanisms ◽  
Influenza Virus Infection ◽  
Asian Strain ◽  
Temporary Inhibition

Mice infected with a non-mouse-adapted Asian strain of influenza A virus suffered an impaired capacity to destroy or remove staphylococci introduced by the respiratory route. This temporary inhibition of local defense mechanisms was of 7 to 10 days' duration. The persistence of staphylococci in the lung following influenza did not appear to alter the nature of the pathologic reaction to influenza virus. The presence of influenza virus infection in the respiratory tract of the mouse did not alter the fate of intravenous staphylococci in the lung or other organs. In 40 to 50 per cent of mice with influenza, purulent bronchopneumonia and infection with Pasteurella and Hemophilus of murine origin were noted. A minority of control animals evidenced such infection. The administration of antimicrobials to which the murine bacteria were susceptible prevented both the appearance of the endogenous infection with Pasteurella or Hemophilus and the purulent sequelae to influenza virus infection. The true picture of uncomplicated bronchopulmonary influenza virus infection was thus separated from the combined virus-bacteria effect otherwise encountered.

scholarly journals Avian Influenza Virus Infection Risk in Humans with Chronic Diseases

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Yaogang Zhong ◽  
Yannan Qin ◽  
Hanjie Yu ◽  
Jingmin Yu ◽  
Haoxiang Wu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Chronic Diseases ◽  
Influenza Virus Infection ◽  
Infection Risk

scholarly journals Influenza “Trains” the Host for Enhanced Susceptibility to Secondary Bacterial Infection

mBio ◽  
2019 ◽  
Vol 10 (3) ◽  
Author(s):  
Kari Ann Shirey ◽  
Darren J. Perkins ◽  
Wendy Lai ◽  
Wei Zhang ◽  
Lurds R. Fernando ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Bacterial Infection ◽  
Bacterial Infections ◽  
Influenza Virus Infection ◽  
Health Concern ◽  
Type I ◽  
Lung Pathology ◽  
Chemokine Production ◽  
Content Type

ABSTRACT We previously reported that the Toll-like receptor 4 (TLR4) antagonist Eritoran blocks acute lung injury (ALI) therapeutically in mouse and cotton rat models of influenza. However, secondary (2°) bacterial infection following influenza virus infection is associated with excess morbidity and mortality. Wild-type (WT) mice infected with mouse-adapted influenza A/Puerto Rico/8/34 virus (PR8) and, 7 days later, with Streptococcus pneumoniae serotype 3 (Sp3) exhibited significantly enhanced lung pathology and lethality that was reversed by Eritoran therapy after PR8 infection but before Sp3 infection. Cotton rats infected with nonadapted pH1N1 influenza virus and then superinfected with methicillin-resistant Staphylococcus aureus also exhibited increased lung pathology and serum high-mobility-group box 1 (HMGB1) levels, both of which were blunted by Eritoran therapy. In mice, PR8 infection suppressed Sp3-induced CXCL1 and CXCL2 mRNA, reducing neutrophil infiltration and increasing the bacterial burden, all of which were reversed by Eritoran treatment. While beta interferon (IFN-β)-deficient (IFN-β−/−) mice are highly susceptible to PR8, they exhibited delayed death upon Sp3 superinfection, indicating that while IFN-β was protective against influenza, it negatively impacted the host response to Sp3. IFN-β-treated WT macrophages selectively suppressed Sp3-induced CXCL1/CXCL2 transcriptionally, as evidenced by reduced recruitment of RNA polymerase II to the CXCL1 promoter. Thus, influenza establishes a “trained” state of immunosuppression toward 2° bacterial infection, in part through the potent induction of IFN-β and its downstream transcriptional regulation of chemokines, an effect reversed by Eritoran. IMPORTANCE Enhanced susceptibility to 2° bacterial infections following infection with influenza virus is a global health concern that accounts for many hospitalizations and deaths, particularly during pandemics. The complexity of the impaired host immune response during 2° bacterial infection has been widely studied. Both type I IFN and neutrophil dysfunction through decreased chemokine production have been implicated as mechanisms underlying enhanced susceptibility to 2° bacterial infections. Our findings support the conclusion that selective suppression of CXCL1/CXCL2 represents an IFN-β-mediated “training” of the macrophage transcriptional response to TLR2 agonists and that blocking of TLR4 therapeutically with Eritoran after influenza virus infection reverses this suppression by blunting influenza-induced IFN-β.

scholarly journals Reconstructing antibody dynamics to estimate the risk of influenza virus infection

2021 ◽  
Author(s):  
Tim Tsang ◽  
Ranawaka Perera ◽  
Vicky Fang ◽  
Jessica Wong ◽  
Eunice Shiu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Bayesian Model ◽  
Influenza Virus Infection ◽  
Fold Increase ◽  
Infection Risk ◽  
Virus Infections ◽  
Younger Adults ◽  
Protection Against Infection ◽  
Antibody Dynamics

Abstract For >70 years, a 4-fold or greater rise in antibody titer has been used to confirm influenza virus infections in paired sera, despite recognition that this heuristic can lack sensitivity. Here we analyze with a novel Bayesian model a large cohort of 2,353 individuals followed for up to 5 years in Hong Kong to characterize influenza antibody dynamics and develop an algorithm to improve the identification of influenza virus infections. After infection, we estimate that hemagglutination-inhibiting (HAI) titers were boosted by 16-fold on average and subsequently decrease by 14% per year. Greater boosting in HAI titer is observed in epidemics with a circulating strain that is different from the previous epidemic. In six epidemics, the infection risks for adults were 3%-19% while the infection risks for children were 1.6-4.4 times higher than that of younger adults. Every two-fold increase in pre-epidemic HAI titer was associated with 19%-58% protection against infection. Among the 1731 infections inferred by our model, around half were missed by the 4-fold rise criteria, suggesting that this criteria underestimates infection risks by 23-70%. The sensitivity and specificity of identifying infections for our approach are 87% (95% CrI: 85%, 89%) and 98% (95% CrI: 97%, 98%) respectively, which are higher than 82% (95% CrI: 80%, 84%) and 96% (95% CrI: 96%, 97%) for using 4-fold rise criteria. Our inferential framework clarifies the contributions of age and pre-epidemic HAI titers to characterize individual infection risk and offers an improved algorithm to identify influenza virus infections.

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