Clearance of Pneumococcal Colonization in Infants Is Delayed through Altered Macrophage Trafficking

Siegel, Steven J.; Tamashiro, Edwin; Weiser, Jeffrey N.

doi:10.1371/journal.ppat.1005004

Cited by 32 publications

(31 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We focused on infant mice because transmission has not been observed among adults, an effect that could be due to the higher dose required to colonize adult mice (22). To further explore the contribution of age at the time of inoculation, mice were infected at age 4, 8, or 12 days and shedding was monitored over the next 5 days (Fig.…”

Section: Resultsmentioning

confidence: 99%

Infant Mouse Model for the Study of Shedding and Transmission during Streptococcus pneumoniae Monoinfection

et al. 2016

Self Cite

View full text Add to dashboard Cite

One of the least understood aspects of the bacterium Streptococcus pneumoniae (pneumococcus) is its transmission from host to host, the critical first step in both the carrier state and the disease state. To date, transmission models have depended on influenza A virus coinfection, which greatly enhances pneumococcal shedding to levels that allow acquisition by a new host. Here, we describe an infant mouse model that can be utilized to study pneumococcal colonization, shedding, and transmission during bacterial monoinfection. Using this model, we demonstrated that the level of bacterial shedding is highest in pups infected intranasally at age 4 days and peaks over the first 4 days postchallenge. Shedding results differed among isolates of five different pneumococcal types. Colonization density was found to be a major factor in the level of pneumococcal shedding and required expression of capsule. Transmission within a litter occurred when there was a high ratio of colonized "index" pups to uncolonized "contact" pups. Transmission was observed for each of the well-colonizing pneumococcal isolates, with the rate of transmission proportional to the level of shedding. This model can be used to examine bacterial and host factors that contribute to pneumococcal transmission without the effects of viral coinfection.T ransmission from one infected individual to another is necessary for most agents of infection. For Streptococcus pneumoniae (the pneumococcus), a leading opportunistic Gram-positive human pathogen, transmission occurs primarily from hosts colonized on the mucosal surfaces of their upper respiratory tract (the carrier state; 1). Bacterial acquisition and colonization of the mucosal surfaces of the nasopharynx by pneumococci are dynamic, transient processes which are generally asymptomatic and occur most commonly during early childhood. Under certain circumstances, however, pneumococci gain access to normally sterile environments within the host, resulting in diseases such as otitis media, pneumonia, sepsis, and meningitis. Acute respiratory infections associated with the pneumococcus represent a significant public health burden, with an estimated 14.5 million cases of serious pneumococcal disease worldwide (2). None of its many disease states, however, is thought to promote pneumococcal contagion (3).While bacterial and host factors contributing to the carrier state have been studied in the natural host and modeled in animals, there is relatively little mechanistic understanding of transmission (4). Person-to-person spread is thought to require close contact, such as within families or day care centers, either directly from nasal secretions or possibly via contact with contaminated surfaces (fomites; 3, 5). Therefore, one of the key steps in pneumococcal contagion involves the exit or shedding of the organism from the respiratory tract of a colonized individual.A factor known to enhance pneumococcal shedding is a concurrent or recent viral respiratory infection (6, 7). Increased rates of carriage associated ...

show abstract

Section: Resultsmentioning

confidence: 99%

Infant Mouse Model for the Study of Shedding and Transmission during Streptococcus pneumoniae Monoinfection

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Mice were colonized with 10 7 CFU of a clinical strain of S. pneumoniae, P1547 (serotype 6A), obtained from Jeff Weiser (NYU School of Medicine) as described previously (27,28). The bacteria were grown in tryptic soy broth medium (Life Technologies) at 37°C and 5% CO 2 until cultures reached log phase, with an optical density at 600 nm (OD 600 ) of between 0.45 and 0.55 (27). Anesthetized mice were euthanized by exsanguination.…”

Section: Methodsmentioning

confidence: 99%

“…Briefly, each PCR mixture contained the following in order to amplify V3 of the 16S rRNA gene by PCR: 5 l of 10ϫ buffer (Life Technologies), 1.5 l of MgCl 2 (50 mM) (Life Technologies), 1 l of deoxynucleoside triphosphate (dNTP) (10 mM) (Invitrogen), 2 l of bovine serum albumin (BSA) (10 mg/ml made in pure water and irradiated for 30 min) (Life Technologies), 5 l of V3F primer (1 M) (27), 5 l of V3R primer (1 M) (27), 0.5 l of Taq polymerase (Life Technologies), and 200 ng of DNA. The reaction then was run for 30 cycles (94°C for 2 min, 94°C for 30 s, 50°C for 30°C, 72°C for 30 s), with a final polymerization step at 72°C for 10 min (Eppendorf).…”

Section: Methodsmentioning

confidence: 99%

Streptococcus pneumoniae Colonization Disrupts the Microbial Community within the Upper Respiratory Tract of Aging Mice

et al. 2016

View full text Add to dashboard Cite

f Nasopharyngeal colonization by the Gram-positive bacterium Streptococcus pneumoniae is a prerequisite for pneumonia and invasive pneumococcal diseases. Colonization is asymptomatic, involving dynamic and complex interplay between commensals, the host immune system, and environmental factors. The elderly are at an increased risk of developing pneumonia, which might be due to changes in the respiratory microbiota that would impact bacterial colonization and persistence within this niche. We hypothesized that the composition of the upper respiratory tract (URT) microbiota changes with age and subsequently can contribute to sustained colonization and inefficient clearance of S. pneumoniae. To test this, we used a mouse model of pneumococcal colonization to compare the composition of the URT microbiota in young, middle-aged, and old mice in the naive state and during the course of colonization using nasal pharyngeal washes. Sequencing of variable region 3 (V3) of the 16S rRNA gene was used to identify changes occurring with age and throughout the course of S. pneumoniae colonization. We discovered that age affects the composition of the URT microbiota and that colonization with S. pneumoniae is more disruptive of preexisting communities in older mice. We have further shown that host-pathogen interactions following S. pneumoniae colonization can impact the populations of resident microbes, including Staphylococcus and Haemophilus. Together, our findings indicate alterations to the URT microbiota could be detrimental to the elderly, resulting in increased colonization of S. pneumoniae and decreased efficiency in its clearance.

show abstract

“…Recruited macrophages utilize a variety of mechanisms to control invading pneumococci. Decreased macrophage trafficking in infants results in delayed clearance of pneumococcal colonization (9). Reducing the bactericidal function of alveolar macrophages with glucocorticoid leads to inhibition of pulmonary pneumococcal clearance in mice (10), while promoting CCL2-mediated macrophage recruitment with macrolides accelerates clearance of nasopharyngeal pneumococcal colonization in mice (11).…”

mentioning

confidence: 99%

Purified Streptococcus pneumoniae Endopeptidase O (PepO) Enhances Particle Uptake by Macrophages in a Toll-Like Receptor 2- and miR-155-Dependent Manner

et al. 2017

View full text Add to dashboard Cite

Insights into the host-microbial virulence factor interaction, especially the immune signaling mechanisms, could provide novel prevention and treatment options for pneumococcal diseases. Streptococcus pneumoniae endopeptidase O (PepO) is a newly discovered and ubiquitously expressed pneumococcal virulence protein. A PepO-mutant strain showed impaired adherence to and invasion of host cells compared with the isogenic wild-type strain. It is still unknown whether PepO is involved in the host defense response to pneumococcal infection. Here, we demonstrated that PepO could enhance phagocytosis of Streptococcus pneumoniae and Staphylococcus aureus by peritoneal exudate macrophages (PEMs). Further studies showed that PepO stimulation upregulated the expression of microRNA-155 (miR-155) in PEMs in a time-and dose-dependent manner. PepO-induced enhanced phagocytosis was decreased in cells transfected with an inhibitor of miR-155, while it was increased in cells transfected with a mimic of miR-155. We also revealed that PepO-induced upregulation of miR-155 in PEMs was mediated by Toll-like receptor 2 (TLR2)-NF-B signaling and that the increased expression of miR-155 downregulated expression of SHIP1. Taken together, these results indicate that PepO induces upregulation of miR-155 in PEMs, contributing to enhanced phagocytosis and host defense response to pneumococci and Staphylococcus aureus.

show abstract

Clearance of Pneumococcal Colonization in Infants Is Delayed through Altered Macrophage Trafficking

Cited by 32 publications

References 43 publications

Infant Mouse Model for the Study of Shedding and Transmission during Streptococcus pneumoniae Monoinfection

Infant Mouse Model for the Study of Shedding and Transmission during Streptococcus pneumoniae Monoinfection

Streptococcus pneumoniae Colonization Disrupts the Microbial Community within the Upper Respiratory Tract of Aging Mice

Purified Streptococcus pneumoniae Endopeptidase O (PepO) Enhances Particle Uptake by Macrophages in a Toll-Like Receptor 2- and miR-155-Dependent Manner

Contact Info

Product

Resources

About