Virus-Induced Changes of the Respiratory Tract Environment Promote Secondary Infections With Streptococcus pneumoniae

Secondary bacterial infections enhance the disease burden of influenza infections substantially. Streptococcus pneumoniae (the pneumococcus) plays a major role in the synergism between bacterial and viral pathogens, which is based on complex interactions between the pathogen and the host immune response. Here, we discuss mechanisms that drive the pathogenesis of a secondary pneumococcal infection after an influenza infection with a focus on how pneumococci senses and adapts to the influenza-modified environment. We briefly summarize what is known regarding secondary bacterial infection in relation to COVID-19 and highlight the need to improve our current strategies to prevent and treat viral bacterial coinfections.

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The Respiratory Commensal Bacterium Dolosigranulum pigrum 040417 Improves the Innate Immune Response to Streptococcus pneumoniae

Microorganisms ◽

10.3390/microorganisms9061324 ◽

2021 ◽

Vol 9 (6) ◽

pp. 1324

Author(s):

Fernanda Raya Tonetti ◽

Mikado Tomokiyo ◽

Ramiro Ortiz Moyano ◽

Sandra Quilodrán-Vega ◽

Hikari Yamamuro ◽

...

Keyword(s):

Immune Response ◽

Streptococcus Pneumoniae ◽

Innate Immune Response ◽

Pneumococcal Infection ◽

Innate Immune ◽

Nasal Administration ◽

Commensal Bacterium ◽

Beneficial Effects ◽

Immunological Mechanisms ◽

Immunomodulatory Properties

Previously, we demonstrated that the nasal administration of Dolosigranulum pigrum 040417 differentially modulated the respiratory innate immune response triggered by the activation of Toll-like receptor 2 in infant mice. In this work, we aimed to evaluate the beneficial effects of D. pigrum 040417 in the context of Streptococcus pneumoniae infection and characterize the role of alveolar macrophages (AMs) in the immunomodulatory properties of this respiratory commensal bacterium. The nasal administration of D. pigrum 040417 to infant mice significantly increased their resistance to pneumococcal infection, differentially modulated respiratory cytokines production, and reduced lung injuries. These effects were associated to the ability of the 040417 strain to modulate AMs function. Depletion of AMs significantly reduced the capacity of the 040417 strain to improve both the reduction of pathogen loads and the protection against lung tissue damage. We also demonstrated that the immunomodulatory properties of D. pigrum are strain-specific, as D. pigrum 030918 was not able to modulate respiratory immunity or to increase the resistance of mice to an S. pneumoniae infection. These findings enhanced our knowledge regarding the immunological mechanisms involved in modulation of respiratory immunity induced by beneficial respiratory commensal bacteria and suggested that particular strains could be used as next-generation probiotics.

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Impact of Influenza on Pneumococcal Vaccine Effectiveness during Streptococcus pneumoniae Infection in Aged Murine Lung

Vaccines ◽

10.3390/vaccines8020298 ◽

2020 ◽

Vol 8 (2) ◽

pp. 298

Author(s):

Ermias Jirru ◽

Stefi Lee ◽

Rebecca Harris ◽

Jianjun Yang ◽

Soo Jung Cho ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Immune Responses ◽

Pneumococcal Vaccine ◽

Influenza A ◽

Secondary Infection ◽

Influenza Infection ◽

Vaccine Effectiveness ◽

Murine Lung ◽

Vaccine Responses ◽

Secondary Infections

Changes in innate and adaptive immune responses caused by viral imprinting can have a significant direct or indirect influence on secondary infections and vaccine responses. The purpose of our current study was to investigate the role of immune imprinting by influenza on pneumococcal vaccine effectiveness during Streptococcus pneumoniae infection in the aged murine lung. Aged adult (18 months) mice were vaccinated with the pneumococcal polyvalent vaccine Pneumovax (5 mg/mouse). Fourteen days post vaccination, mice were instilled with PBS or influenza A/PR8/34 virus (3.5 × 102 PFU). Control and influenza-infected mice were instilled with PBS or S. pneumoniae (1 × 103 CFU, ATCC 6303) on day 7 of infection and antibacterial immune responses were assessed in the lung. Our results illustrate that, in response to a primary influenza infection, there was diminished bacterial clearance and heightened production of pro-inflammatory cytokines, such as IL6 and IL1β. Vaccination with Pneumovax decreased pro-inflammatory cytokine production by modulating NFҡB expression; however, these responses were significantly diminished after influenza infection. Taken together, the data in our current study illustrate that immune imprinting by influenza diminishes pneumococcal vaccine efficacy and, thereby, may contribute to increased susceptibility of older persons to a secondary infection with S. pneumoniae.

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Cigarette Smoke Attenuates the Nasal Host Response to Streptococcus pneumoniae and Predisposes to Invasive Pneumococcal Disease in Mice

Infection and Immunity ◽

10.1128/iai.01504-15 ◽

2016 ◽

Vol 84 (5) ◽

pp. 1536-1547 ◽

Cited By ~ 14

Author(s):

Pamela Shen ◽

Mathieu C. Morissette ◽

Gilles Vanderstocken ◽

Yang Gao ◽

Muhammad Hassan ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Cigarette Smoke ◽

Invasive Pneumococcal Disease ◽

Bacterial Infections ◽

Pneumococcal Disease ◽

Pneumococcal Infection ◽

Cigarette Smoke Exposure ◽

Upper Respiratory Tract ◽

Content Type ◽

Pneumococcal Colonization

Streptococcus pneumoniaeis a leading cause of invasive bacterial infections, with nasal colonization an important first step in disease. While cigarette smoking is a strong risk factor for invasive pneumococcal disease, the underlying mechanisms remain unknown. This is partly due to a lack of clinically relevant animal models investigating nasal pneumococcal colonization in the context of cigarette smoke exposure. We present a model of nasal pneumococcal colonization in cigarette smoke-exposed mice and document, for the first time, that cigarette smoke predisposes to invasive pneumococcal infection and mortality in an animal model. Cigarette smoke increased the risk of bacteremia and meningitis without prior lung infection. Mechanistically, deficiency in interleukin 1α (IL-1α) or platelet-activating factor receptor (PAFR), an important host receptor thought to bind and facilitate pneumococcal invasiveness, did not rescue cigarette smoke-exposed mice from invasive pneumococcal disease. Importantly, we observed cigarette smoke to attenuate nasal inflammatory mediator expression, particularly that of neutrophil-recruiting chemokines, normally elicited by pneumococcal colonization. Smoking cessation during nasal pneumococcal colonization rescued nasal neutrophil recruitment and prevented invasive disease in mice. We propose that cigarette smoke predisposes to invasive pneumococcal disease by suppressing inflammatory processes of the upper respiratory tract. Given that smoking prevalence remains high worldwide, these findings are relevant to the continued efforts to reduce the invasive pneumococcal disease burden.

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A systems and treatment perspective of models of influenza virus-induced host responses

10.1101/368241 ◽

2018 ◽

Author(s):

Ericka Mochan ◽

Emily Ackerman ◽

Jason E. Shoemaker

Keyword(s):

Immune Response ◽

Immune Modulation ◽

Influenza Infection ◽

Risk Groups ◽

Host Responses ◽

Complex Interactions ◽

Current State ◽

Severe Influenza ◽

Future Work ◽

Model Virus

AbstractSevere influenza infections are often characterized as having unique host responses (e.g. early, severe hypercytokinemia). Neuraminidase inhibitors can be effective in controlling the severe symptoms of influenza but are often not administered until late in the infection. Several studies suggest that immune modulation may offer protection to high risk groups. Here, we review the current state of mathematical models of influenza-induced host responses. Selecting three models with conserved immune response components, we determine if the immune system components which most affect virus replication when perturbed are conserved across the models. We also test each model’s response to a pre-induction of interferon before the virus is administered. We find that each model emphasizes the importance of controlling the infected cell population to control viral replication. Moreover, our work shows that the structure of current models does not allow for significant responses to increased interferon concentrations. These results suggest that the current library of available published models of influenza infection does not adequately represent the complex interactions of the virus, interferon, and other aspects of the immune response. Specifically, the method used to model virus-resistant cells may need to be adapted in future work to more realistically represent the immune response to viral infection.

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Involvement of the platelet-activating factor receptor in host defense against Streptococcus pneumoniae during postinfluenza pneumonia

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00050.2005 ◽

2006 ◽

Vol 290 (1) ◽

pp. L194-L199 ◽

Cited By ~ 57

Author(s):

Koenraad F. van der Sluijs ◽

Leontine J. R. van Elden ◽

Monique Nijhuis ◽

Rob Schuurman ◽

Sandrine Florquin ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Influenza A ◽

Bacterial Infections ◽

Influenza Infection ◽

Platelet Activating Factor ◽

Severe Pneumonia ◽

Tnf Α ◽

Platelet Activating Factor Receptor ◽

Bacterial Outgrowth

Although influenza infection alone may lead to pneumonia, secondary bacterial infections are a much more common cause of pneumonia. Streptococcus pneumoniae is the most frequently isolated causative pathogen during postinfluenza pneumonia. Considering that S. pneumoniae utilizes the platelet-activating factor receptor (PAFR) to invade the respiratory epithelium and that the PAFR is upregulated during viral infection, we here used PAFR gene-deficient (PAFR−/−) mice to determine the role of this receptor during postinfluenza pneumococcal pneumonia. Viral clearance was similar in wild-type and PAFR−/− mice, and influenza virus was completely removed from the lungs at the time mice were inoculated with S. pneumoniae ( day 14 after influenza infection). PAFR−/− mice displayed a significantly reduced bacterial outgrowth in their lungs, a diminished dissemination of the infection, and a prolonged survival. Pulmonary levels of IL-10 and KC were significantly lower in PAFR−/− mice, whereas IL-6 and TNF-α were only trendwise lower. These data indicate that the pneumococcus uses the PAFR leading to severe pneumonia in a host previously exposed to influenza A.

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A Systems and Treatment Perspective of Models of Influenza Virus-Induced Host Responses

Processes ◽

10.3390/pr6090138 ◽

2018 ◽

Vol 6 (9) ◽

pp. 138 ◽

Cited By ~ 1

Author(s):

Ericka Mochan ◽

Emily Ackerman ◽

Jason Shoemaker

Keyword(s):

Immune Response ◽

Immune Modulation ◽

Influenza Infection ◽

Risk Groups ◽

Host Responses ◽

Complex Interactions ◽

Current State ◽

Severe Influenza ◽

Future Work ◽

Model Virus

Severe influenza infections are often characterized as having unique host responses (e.g., early, severe hypercytokinemia). Neuraminidase inhibitors can be effective in controlling the severe symptoms of influenza but are often not administered until late in the infection. Several studies suggest that immune modulation may offer protection to high risk groups. Here, we review the current state of mathematical models of influenza-induced host responses. Selecting three models with conserved immune response components, we determine if the immune system components which most affect virus replication when perturbed are conserved across the models. We also test each model’s response to a pre-induction of interferon before the virus is administered. We find that each model emphasizes the importance of controlling the infected cell population to control viral replication. Moreover, our work shows that the structure of current models does not allow for significant responses to increased interferon concentrations. These results suggest that the current library of available published models of influenza infection does not adequately represent the complex interactions of the virus, interferon, and other aspects of the immune response. Specifically, the method used to model virus-resistant cells may need to be adapted in future work to more realistically represent the immune response to viral infection.

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Co-infection of Streptococcus pneumoniae in Respiratory Infections Caused by SARS-CoV-2

Biointerface Research in Applied Chemistry ◽

10.33263/briac114.1217012177 ◽

2021 ◽

Vol 11 (4) ◽

pp. 12170-12177

Keyword(s):

Streptococcus Pneumoniae ◽

Bacterial Infections ◽

Hospital Admissions ◽

Respiratory Infections ◽

Pneumococcal Infection ◽

Pneumococcal Vaccination ◽

Bacterial Pathogen ◽

Diagnostic Methods ◽

Clinical Test ◽

Influenza Pandemics

Viral respiratory infections are often associated with bacterial co-infections that often lead to increased severity and mortality of the disease. During the recent pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), hospitalized patients reported developing secondary bacterial infections ranging from 0 to 40% of the cases. In the previous influenza pandemics, Streptococcus pneumoniae was the most isolated bacterial pathogen causing increased mortality in patients affected by viral pneumonia. Due to the difficulty to detect pneumococcal infection in SARS-CoV-2 patients by a rapid clinical test, the real prevalence of S. pneumoniae might be underestimated, and only a few cases have been documented so far. It has been estimated that 90% of patients admitted to the Intensive Care Unit are empirically treated with antimicrobial. The application of more rapid and sensitive diagnostic methods could help with targeted antibiotic therapy. Additionally, pneumococcal vaccination of high-risk individuals could reduce bacterial pneumonia, hospital admissions, and comorbidities associated with serious illness.

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Organoids to Dissect Gastrointestinal Virus–Host Interactions: What Have We Learned?

Viruses ◽

10.3390/v13060999 ◽

2021 ◽

Vol 13 (6) ◽

pp. 999

Author(s):

Sue E. Crawford ◽

Sasirekha Ramani ◽

Sarah E. Blutt ◽

Mary K. Estes

Keyword(s):

Cell Types ◽

Human Infection ◽

Viral Pathogens ◽

Host Interactions ◽

Complex Interactions ◽

Microbe Interactions ◽

Host Microbe Interactions ◽

Human Intestinal Epithelium ◽

Human Viruses ◽

Human Infections

Historically, knowledge of human host–enteric pathogen interactions has been elucidated from studies using cancer cells, animal models, clinical data, and occasionally, controlled human infection models. Although much has been learned from these studies, an understanding of the complex interactions between human viruses and the human intestinal epithelium was initially limited by the lack of nontransformed culture systems, which recapitulate the relevant heterogenous cell types that comprise the intestinal villus epithelium. New investigations using multicellular, physiologically active, organotypic cultures produced from intestinal stem cells isolated from biopsies or surgical specimens provide an exciting new avenue for understanding human specific pathogens and revealing previously unknown host–microbe interactions that affect replication and outcomes of human infections. Here, we summarize recent biologic discoveries using human intestinal organoids and human enteric viral pathogens.

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Antimicrobial resistance profile and multidrug resistance patterns of Streptococcus pneumoniae isolates from patients suspected of pneumococcal infections in Ethiopia

Annals of Clinical Microbiology and Antimicrobials ◽

10.1186/s12941-021-00432-z ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Bekele Sharew ◽

Feleke Moges ◽

Gizachew Yismaw ◽

Wondwossen Abebe ◽

Surafal Fentaw ◽

...

Keyword(s):

Multidrug Resistance ◽

Streptococcus Pneumoniae ◽

Antimicrobial Resistance ◽

Addis Ababa ◽

Pneumococcal Infection ◽

Test Method ◽

Resistance Testing ◽

Global Public Health ◽

Pneumococcal Infections ◽

Resistance Patterns

Abstract Background Antimicrobial-resistant strains of Streptococcus pneumoniae have become one of the greatest challenges to global public health today and inappropriate use of antibiotics and high level of antibiotic use is probably the main factor driving the emergence of resistance worldwide. The aim of this study is, therefore, to assess the antimicrobial resistance profiles and multidrug resistance patterns of S. pneumoniae isolates from patients suspected of pneumococcal infections in Ethiopia. Methods A hospital-based prospective study was conducted from January 2018 to December 2019 at Addis Ababa city and Amhara National Region State Referral Hospitals. Antimicrobial resistance tests were performed from isolates of S. pneumoniae that were collected from pediatric and adult patients. Samples (cerebrospinal fluid, blood, sputum, eye discharge, ear discharge, and pleural and peritoneal fluids) from all collection sites were initially cultured on 5% sheep blood agar plates and incubated overnight at 37 °C in a 5% CO2 atmosphere. Streptococcus pneumoniae was identified and confirmed by typical colony morphology, alpha-hemolysis, Gram staining, optochin susceptibility, and bile solubility test. Drug resistance testing was performed using the E-test method according to recommendations of the Clinical and Laboratory Standards Institute. Results Of the 57 isolates, 17.5% were fully resistant to penicillin. The corresponding value for both cefotaxime and ceftriaxone was 1.8%. Resistance rates to erythromycin, clindamycin, tetracycline, chloramphenicol and trimethoprim-sulfamethoxazole were 59.6%, 17.5%, 38.6%, 17.5 and 24.6%, respectively. Multidrug resistance (MDR) was seen in 33.3% isolates. The most common pattern was co-resistance to penicillin, erythromycin, clindamycin, and tetracycline. Conclusions Most S. pneumoniae isolates were susceptible to ceftriaxone and cefotaxime. Penicillin has been used as a drug of choice for treating S. pneumoniae infection. However, antimicrobial resistance including multidrug resistance was observed to several commonly used antibiotics including penicillin. Hence, it is important to periodically monitor the antimicrobial resistance patterns to select empirical treatments for better management of pneumococcal infection.

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Trace Elements as Immunoregulators in SARS-CoV-2 and Other Viral Infections

Indian Journal of Clinical Biochemistry ◽

10.1007/s12291-021-00961-6 ◽

2021 ◽

Author(s):

Karthick Dharmalingam ◽

Amandeep Birdi ◽

Sojit Tomo ◽

Karli Sreenivasulu ◽

Jaykaran Charan ◽

...

Keyword(s):

Immune Response ◽

Trace Elements ◽

Viral Entry ◽

Viral Infections ◽

Inhibitory Effect ◽

Antioxidants Activity ◽

Host Immune Responses ◽

Complex Interactions ◽

Downstream Processes

AbstractNutritional deficiency is associated with impaired immunity and increased susceptibility to infections. The complex interactions of trace elements with the macromolecules trigger the effective immune response against the viral diseases. The outcome of various viral infections along with susceptibility is affected by trace elements such as zinc, selenium, iron, copper, etc. due to their immuno-modulatory effects. Available electronic databases have been comprehensively searched for articles published with full text available and with the key words “Trace elements”, “COVID-19”, “Viral Infections” and “Immune Response” (i.e. separately Zn, Se, Fe, Cu, Mn, Mo, Cr, Li, Ni, Co) appearing in the title and abstract. On the basis of available articles we have explored the role of trace elements in viral infections with special reference to COVID-19 and their interactions with the immune system. Zinc, selenium and other trace elements are vital to triggerTH1 cells and cytokine-mediated immune response for substantial production of proinflammatory cytokines. The antiviral activity of some trace elements is attributed to their inhibitory effect on viral entry, replication and other downstream processes. Trace elements having antioxidants activity not only regulate host immune responses, but also modify the viral genome. Adequate dietary intake of trace elements is essential for activation, development, differentiation and numerous functions.

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