Pneumococcal Pneumonia Infections Research Articles

Immunomodulation of susceptibility to pneumococcal pneumonia infection in mouse lungs exposed to carbon nanoparticles via dysregulation of innate and adaptive immune responses

Carbon nanotubes (CNTs) are emerging pollutants of occupational and environmental health concern. While toxicological mechanisms of CNTs are emerging, there is paucity of information on their modulatory effects on susceptibility to infections. Here, we investigated cellular and molecular events underlying the effect of multi-walled CNT (MWCNT) exposure on susceptibility to Streptococcus pneumoniae infection in our 28-day sub-chronic exposure mouse model. Data indicated reduced phagocytic function in alveolar macrophages (AMs) from MWCNT-exposed lungs evidenced by lower pathogen uptake in 1-h infection assay. At 24-h post-infection, intracellular pathogen count in exposed AMs showed 2.5 times higher net increase (2-fold in vehicle- versus 5-fold in MWCNT-treated), indicating a greater rate of intracellular multiplication and/or survival due to MWCNT exposure. AMs from MWCNT-exposed lungs exhibited downregulation of pathogen-uptake receptors CD163, Phosphatidyl-serine receptor (Ptdsr), and Macrophage scavenger receptors class A type 1 (Msr1) and type 2 (MSr2). In whole lung, MWCNT exposure shifted the macrophage polarization state towards the immunosuppressive phenotype M2b and increased the CD11c+ dendritic cell population required to activate the adaptive immune response. Notably, the MWCNT pre-exposure dysregulated T-cell immunity, evidenced by diminished CD4 and Th17 response, and exacerbated Th1 and Treg responses (skewed Th17/Treg ratio), thereby favoring the pneumococcal infection. Overall, these findings indicated that MWCNT exposure compromises both innate and adaptive immunity leading to diminished host lung defense against pneumonia infection. To our knowledge, this is the first report on an immunomodulatory role of CNT pre-exposure on pneumococcal infection susceptibility due to dysregulation of both innate and adaptive immunity targets.

Comparative transcriptomic and proteomic signature of lung alveolar macrophages reveals the integrin CD11b as a regulatory hub during pneumococcal pneumonia infection.

Streptococcus pneumoniae is one of the main causes of community-acquired infections in the lung alveoli in children and the elderly. Alveolar macrophages (AM) patrol alveoli in homeostasis and under infectious conditions. However, the molecular adaptations of AM upon infections with Streptococcus pneumoniae are incompletely resolved. We used a comparative transcriptomic and proteomic approach to provide novel insights into the cellular mechanism that changes the molecular signature of AM during lung infections. Using a tandem mass spectrometry approach to murine cell-sorted AM, we revealed significant proteomic changes upon lung infection with Streptococcus pneumoniae. AM showed a strong neutrophil-associated proteomic signature, such as expression of CD11b, MPO, neutrophil gelatinases, and elastases, which was associated with phagocytosis of recruited neutrophils. Transcriptomic analysis indicated intrinsic expression of CD11b by AM. Moreover, comparative transcriptomic and proteomic profiling identified CD11b as the central molecular hub in AM, which influenced neutrophil recruitment, activation, and migration. In conclusion, our study provides novel insights into the intrinsic molecular adaptations of AM upon lung infection with Streptococcus pneumoniae and reveals profound alterations critical for effective antimicrobial immunity.

Effect of vaccination on non-integer dynamics of pneumococcal pneumonia infection

Pneumococcal pneumonia is a contagious, possibly fatal bacterial lung infection that can strike at any time and in any place. It can land you in the hospital and possibly put your life in jeopardy in severe situations. Pneumonia can range from a minor illness to a major or life-threatening infection and it can even be fatal. Therefore, it is of great importance to conceptualize the transmission phenomena of this dangerous infection and to provide control interventions. Here, an epidemic model to conceptualize the transmission phenomena of pneumococcal pneumonia with vaccination and treatment factors is structured. The equilibria of the model are inspected and the reproduction parameter (indicated by ℛ0) is determined. Stability results for the equilibria of the system have been proved. The reproduction parameters of the scheme are analyzed numerically with the variation of various input parameters. Moreover, adequate conditions for the uniqueness and existence of the solution to the hypothesized problem of pneumococcal pneumonia infection have been proved. Different simulations of the recommended pneumococcal pneumonia model are performed by changing the input factors to study the complicated dynamics of pneumococcal pneumonia infection with the influence of different input parameters of the system. This article discusses the system's dynamic behavior in order to develop effective infection control policies. Important changes have been observed when the order of the fractional derivative is decreased. This study recommended different factors for the reduction of pneumococcal pneumonia to the policymakers in the community.

Fractional order of pneumococcal pneumonia infection model with Caputo Fabrizio operator

In this study, we present the Pneumococcal Pneumonia infection model using fractional order derivatives in the Caputo-Fabrizio sense. We use fixed-point theory to prove the existence of the solution and investigate the uniqueness of the model variables. The fractional Adams-Bashforth method is used to compute an iterative solution to the model. Finally, using the model parameter values to explain the importance of the arbitrary fractional order derivative, the numerical results are presented.

Risk modelling the mortality impact of antimicrobial resistance in secondary pneumococcal pneumonia infections during the 2009 influenza pandemic

ObjectivesThe aim of this study was to estimate the impact of antimicrobial resistance (AMR) in secondary pneumococcal pneumonia infections on global mortality during the 2009 influenza pandemic, to estimate future pandemic mortality risk and to inform pandemic preparedness. MethodsRisk analysis modelling was conducted using a multivariate risk formula. Literature reviews were conducted to generate global central estimates for each of the parameters of the risk formula in relation to the 2009 influenza pandemic, secondary pneumococcal pneumonia, rates of AMR, and pneumococcal vaccine efficacy as a component of pandemic preparedness. ResultsGlobal Streptococcus pneumoniae AMR was estimated at 21.8% to 27.6%, and contributed to 1.8% to 2.3% of deaths during the 2009 influenza pandemic. When directly applied to mortality due to multidrug resistance, pneumococcal vaccination could potentially prevent 1277 to 3754 deaths and could have reduced mortality from multidrug-resistant S. pneumoniae to 1% to 1.2%. ConclusionsAMR in secondary pneumococcal infections contributed towards a small percentage of the global mortality during the 2009 influenza pandemic. Increased S. pneumoniae AMR could result in a three- to four-fold rise in mortality due to secondary pneumococcal infections in future influenza pandemics. Pneumococcal vaccination has an important role in preventing pneumococcal co-infections and combating AMR in all populations, and should be considered a key component of influenza pandemic preparedness or early action plans.

A Mathematical Model of Treatment and Vaccination Interventions of Pneumococcal Pneumonia Infection Dynamics

Streptococcus pneumoniae is one of the leading causes of serious morbidity and mortality worldwide, especially in young children and the elderly. In this study, a model of the spread and control of bacterial pneumonia under public health interventions that involve treatment and vaccination is formulated. It is found out that the model exhibits the disease-free and endemic equilibria. The disease-free equilibrium is stable if and only if the basic reproduction number R0<1 and the disease will be wiped out of the population. For R0≥1, the endemic equilibrium is globally stable and the disease persists. We infer the effect of these interventions on the dynamics of the pneumonia through sensitivity analysis on the effective reproduction number Re, from which it is revealed that treatment and vaccination interventions combined can eradicate pneumonia infection. Numerical simulation to illustrate the analytical results and establish the long term behavior of the disease is done. The impact of pneumonia infection control strategies is investigated. It is revealed that, with treatment and vaccination interventions combined, pneumonia can be wiped out. However, with treatment intervention alone, pneumonia persists in the population.

Alcohol and lung injury and immunity.

Annually, excessive alcohol use accounts for more than $220 billion in economic costs and 80,000 deaths, making excessive alcohol use the third leading lifestyle-related cause of death in the US. Patients with an alcohol-use disorder (AUD) also have an increased susceptibility to respiratory pathogens and lung injury, including a 2-4-fold increased risk of acute respiratory distress syndrome (ARDS). This review investigates some of the potential mechanisms by which alcohol causes lung injury and impairs lung immunity. In intoxicated individuals with burn injuries, activation of the gut-liver axis drives pulmonary inflammation, thereby negatively impacting morbidity and mortality. In the lung, the upper airway is the first checkpoint to fail in microbe clearance during alcohol-induced lung immune dysfunction. Brief and prolonged alcohol exposure drive different post-translational modifications of novel proteins that control cilia function. Proteomic approaches are needed to identify novel alcohol targets and post-translational modifications in airway cilia that are involved in alcohol-dependent signal transduction pathways. When the upper airway fails to clear inhaled pathogens, they enter the alveolar space where they are primarily cleared by alveolar macrophages (AM). With chronic alcohol ingestion, oxidative stress pathways in the AMs are stimulated, thereby impairing AM immune capacity and pathogen clearance. The epidemiology of pneumococcal pneumonia and AUDs is well established, as both increased predisposition and illness severity have been reported. AUD subjects have increased susceptibility to pneumococcal pneumonia infections, which may be due to the pro-inflammatory response of AMs, leading to increased oxidative stress.

Troponin I Levels Increase After Experimental Pneumococcal Pneumonia Infection in a Nonhuman Primate Model

Troponin I Levels Increase After Experimental Pneumococcal Pneumonia Infection in a Nonhuman Primate Model

Pneumococcal pneumonia infection is associated with end-stage renal disease in adult hospitalized patients

Pneumococcal disease leads to renal complications ranging from persistent proteinuria to end-stage renal disease (ESRD) in pediatric patients. However, long-term renal effects after pneumococcal pneumonia infection in adult patients remains largely unknown. To evaluate this we conducted a population-based retrospective cohort study consisting of 18,733 adult patients at the time of pneumococcal pneumonia diagnosis, using claims data from Taiwan's National Health Insurance Research Database (NHIRD) with a comparison cohort of 73,409 age- and gender-matched patients without pneumococcal pneumonia. The overall incidence rate ratio of ESRD was 23% higher in those with pneumococcal pneumonia than in those without pneumococcal pneumonia (5.26 vs. 3.10 per 1000 person-years), with an adjusted hazard ratio of 1.14 (95% confidence interval 1.01-1.29). In addition, the risk of developing ESRD was associated with covariates including age, gender, chronic kidney disease, diabetes mellitus, hypertension, hyperlipidemia, chronic obstructive pulmonary disease, and heart failure. The ESRD cumulative incidence curve showed a considerably higher risk of ESRD in those with pneumococcal pneumonia than in those without pneumococcal pneumonia (significant by log-rank test). Thus, pneumococcal pneumonia may be associated with an increased risk of ESRD in adult patients. A long-term follow-up of renal function is recommended for adult hospitalized patients with pneumococcal pneumonia infection.

A mathematical model of intrahost pneumococcal pneumonia infection dynamics in murine strains

The seriousness of pneumococcal pneumonia in mouse models has been shown to depend both on bacterial serotype and murine strain. We here present a simple ordinary differential equation model of the intrahost immune response to bacterial pneumonia that is capable of capturing diverse experimentally determined responses of various murine strains. We discuss the main causes of such differences while accounting for the uncertainty in the estimation of model parameters. We model the bacterial population in both the lungs and blood, the cellular death caused by the infection, and the activation and immigration of phagocytes to the infected tissue. The ensemble model suggests that inter-strain differences in response to streptococcus pneumonia inoculation reside in the strength of nonspecific immune response and the rate of extrapulmonary phagocytosis.

Diagnostic Usefulness of Ribosomal Protein L7/L12 for Pneumococcal Pneumonia in a Mouse Model

The capsular antigen detection (CAD) kit is widely used in clinics to detect Streptococcus pneumoniae infection from urine, because it is rapid, convenient, and effective. However, there are several disadvantages, including false-positive results in children colonized with S. pneumoniae and prolonged positive readings even after the bacteria have been cleared. RP-L7/L12 is a component of the 50S ribosome that is abundant in all bacteria and is specific for each bacterial species. We investigated whether RP-L7/L12 could be used to accurately diagnose pneumococcal pneumonia infection in mouse models of pneumonia and colonization generated by infecting CBA/JN or CBA/N mice, respectively, with S. pneumoniae strain 741. RP-L7/L12 detection by enzyme-linked immunosorbent assay accurately assessed active lung infection, as RP-L7/L12 levels decreased simultaneously with the bacterial lung burden after imipenem administration in the pneumonia mouse model. Based on the data, antibodies detecting RP-L7/L12 were applied to rapid immunochromatographic strips (ICS) for urine sample testing. When we compared the ICS test with the CAD kit in the pneumonia model, the results correlated well. Interestingly, however, when the lung bacterial burden became undetectable after antibiotic treatment, the ICS test was correspondingly negative, even though the same samples tested by the CAD kit remained positive. Similarly, while the ICS test exhibited negative results in the nasal colonization model, the CAD kit demonstrated positive results. Bacterial RP-L7/L12 may be a promising target for the development of new methods to diagnose infectious disease. Further studies are warranted to determine whether such a test could be useful in children.

Genotypes and Related Factors Reflecting Macrolide Resistance in Pneumococcal Pneumonia Infections in Japan

Although macrolide-resistant Streptococcus pneumoniae strains possessing either the ermB or mefA gene are very common in Japan, clinical and microbial factors in community-acquired pneumonia (CAP) caused by different macrolide resistance genotypes have not been evaluated. A multicenter study of CAP caused by S. pneumoniae was performed in Japan from 2003 to 2005. A total of 156 isolates were tested for susceptibility to antibiotics correlated with ermB and mefA genotyping. Independent relationships between tested variables and possession of either the ermB or the mefA gene were identified. Of 156 isolates, 127 (81.4%) were resistant to erythromycin, with the following distribution of resistance genotypes: ermB alone (50.0%), mefA alone (23.7%), and both ermB and mefA (7.1%). All isolates were susceptible to telithromycin. By multivariate analysis, oxygen saturation of <90% on admission increased the risk for ermB-positive pneumococcal pneumonia (odds ratio [OR]=11.1; 95% confidence interval [CI]=1.30 to 95.0; P=0.03), but there were no associations with mefA or with ermB mefA positivity. Penicillin nonsusceptibility was associated with mefA-positive and with ermB- and mefA-positive isolates (OR=14.2; 95% CI=4.27 to 46.9; P<0.0001 and P<0.0001, respectively) but not with ermB-positive isolates. The overall patient mortality was 5.1%. Mortality, the duration of hospitalization, and the resolution of several clinical markers were not associated with the different erythromycin resistance genotypes. In Japan, S. pneumoniae with erythromycin resistance or possession of ermB, mefA, or both genes was highly prevalent in patients with CAP. The risk factors for ermB-positive, mefA-positive, and double ermB-mefA-positive pneumococcal pneumonia were different, but the clinical outcomes did not differ.