scholarly journals Early Innate Immunity to Bacterial Infection in the Lung Is Regulated Systemically by the Commensal Microbiota via Nod-Like Receptor Ligands

2014 ◽  
Vol 82 (11) ◽  
pp. 4596-4606 ◽  
Author(s):  
Thomas B. Clarke
Keyword(s):  
Innate Immunity ◽  
Bacterial Infection ◽  
Muramyl Dipeptide ◽  
Upper Respiratory Tract ◽  
Host Defenses ◽  
Receptor Ligands ◽  
Content Type ◽  
Commensal Microbiota ◽  
Intestinal Pathogens ◽  
Upper Respiratory

ABSTRACTThe commensal microbiota is a major regulator of the immune system. The majority of commensal bacteria inhabit the gastrointestinal tract and are known to regulate local mucosal defenses against intestinal pathogens. There is growing appreciation that the commensal microbiota also regulates immune responses at extraintestinal sites. Currently, however, it is unclear how this influences host defenses against bacterial infection outside the intestine. Microbiota depletion caused significant defects in the early innate response to lung infection by the major human pathogenKlebsiella pneumoniae. After microbiota depletion, early clearance ofK. pneumoniaewas impaired, and this could be rescued by administration of bacterial Nod-like receptor (NLR) ligands (the NOD1 ligand MurNAcTriDAPand NOD2 ligand muramyl dipeptide [MDP]) but not bacterial Toll-like receptor (TLR) ligands. Importantly, NLR ligands from the gastrointestinal, but not upper respiratory, tract rescued host defenses in the lung. Defects in early innate immunity were found to be due to reduced reactive oxygen species-mediated killing of bacteria by alveolar macrophages. These data show that bacterial signals from the intestine have a profound influence on establishing the levels of antibacterial defenses in distal tissues.

scholarly journals Generation and Evaluation of a Glaesserella (Haemophilus) parasuis Capsular Mutant

2020 ◽  
Vol 88 (5) ◽  
Author(s):  
Kirsten C. Eberle ◽  
Samantha J. Hau ◽  
Shi-Lu Luan ◽  
Lucy A. Weinert ◽  
Judith A. Stasko ◽  
...  
Keyword(s):  
Capsular Polysaccharide ◽  
Natural Transformation ◽  
Systemic Disease ◽  
Haemophilus Parasuis ◽  
Upper Respiratory Tract ◽  
Content Type ◽  
Host Interaction ◽  
Challenge Study ◽  
Increased Sensitivity ◽  
Upper Respiratory

ABSTRACT Glaesserella (Haemophilus) parasuis is a commensal bacterium of the upper respiratory tract in pigs and also the causative agent of Glässer’s disease, which causes significant morbidity and mortality in pigs worldwide. Isolates are characterized into 15 serovars by their capsular polysaccharide, which has shown a correlation with isolate pathogenicity. To investigate the role the capsule plays in G. parasuis virulence and host interaction, a capsule mutant of the serovar 5 strain HS069 was generated (HS069Δcap) through allelic exchange following natural transformation. HS069Δcap was unable to cause signs of systemic disease during a pig challenge study and had increased sensitivity to complement killing and phagocytosis by alveolar macrophages. Compared with the parent strain, HS069Δcap produced more robust biofilm and adhered equivalently to 3D4/31 cells; however, it was unable to persistently colonize the nasal cavity of inoculated pigs, with all pigs clearing HS069Δcap by 5 days postchallenge. Our results indicate the importance of the capsular polysaccharide to G. parasuis virulence as well as nasal colonization in pigs.

scholarly journals Identification of Pneumococcal Factors Affecting Pneumococcal Shedding Shows that thedltLocus Promotes Inflammation and Transmission

mBio ◽  
2019 ◽  
Vol 10 (3) ◽  
Author(s):  
M. Ammar Zafar ◽  
Alexandria J. Hammond ◽  
Shigeto Hamaguchi ◽  
Weisheng Wu ◽  
Masamitsu Kono ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Respiratory Tract ◽  
Capsular Polysaccharide ◽  
Inflammatory Responses ◽  
Transposon Mutagenesis ◽  
Respiratory Pathogen ◽  
Invasive Infection ◽  
Upper Respiratory Tract ◽  
Content Type ◽  
Upper Respiratory

ABSTRACTHost-to-host transmission is a necessary but poorly understood aspect of microbial pathogenesis. Herein, we screened a genomic library of mutants of the leading respiratory pathogenStreptococcus pneumoniaegenerated by mariner transposon mutagenesis (Tn-Seq) to identify genes contributing to its exit or shedding from the upper respiratory tract (URT), the limiting step in the organism’s transmission in an infant mouse model. Our analysis focused on genes affecting the bacterial surface that directly impact interactions with the host. Among the multiple factors identified was thedltlocus, which addsd-alanine onto lipoteichoic acids (LTA) and thereby increases Toll-like receptor 2-mediated inflammation and resistance to antimicrobial peptides. The more robust proinflammatory response in the presence ofd-alanylation promotes secretions that facilitate pneumococcal shedding and allows for transmission. Expression of thedltlocus is controlled by the CiaRH system, which senses cell wall stress in response to antimicrobial activity, including in response to lysozyme, the most abundant antimicrobial along the URT mucosa. Accordingly, in alysM−/−host, there was no longer an effect of thedltlocus on pneumococcal shedding. Thus, our findings demonstrate how a pathogen senses the URT milieu and then modifies its surface characteristics to take advantage of the host response for transit to another host.IMPORTANCEStreptococcus pneumoniae(the pneumococcus) is a common cause of respiratory tract and invasive infection. The overall effectiveness of immunization with the organism’s capsular polysaccharide depends on its ability to block colonization of the upper respiratory tract and thereby prevent host-to-host transmission. Because of the limited coverage of current pneumococcal vaccines, we carried out an unbiasedin vivotransposon mutagenesis screen to identify pneumococcal factors other than its capsular polysaccharide that affect transmission. One such candidate was expressed by thedltlocus, previously shown to addd-alanine onto the pneumococcal lipoteichoic acid present on the bacterial cell surface. This modification protects against host antimicrobials and augments host inflammatory responses. The latter increases secretions and bacterial shedding from the upper respiratory tract to allow for transmission. Thus, this study provides insight into a mechanism employed by the pneumococcus to successfully transit from one host to another.

scholarly journals The Interleukins Orchestrate Mucosal Immune Responses to Salmonella Infection in the Intestine

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3492
Author(s):  
Fu-Chen Huang
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Natural Killer ◽  
Adaptive Immunity ◽  
Alternative Therapy ◽  
Muramyl Dipeptide ◽  
Protective Effects ◽  
Salmonella Infection ◽  
Intestinal Pathogens ◽  
Anti Inflammatory

Salmonella infection remains one of the major public health problems in the world, with increasing resistance to antibiotics. The resolution is to explore the pathogenesis of the infection and search for alternative therapy other than antibiotics. Immune responses to Salmonella infection include innate and adaptive immunity. Flagellin or muramyl dipeptide from Salmonella, recognized by extracellular Toll-like receptors and intracellular nucleotide-binding oligomerization domain2, respectively, induce innate immunity involving intestinal epithelial cells, neutrophils, macrophages, dendric cells and lymphocytes, including natural killer (NK) and natural killer T (NKT) cells. The cytokines, mostly interleukins, produced by the cells involved in innate immunity, stimulate adaptive immunity involving T and B cells. The mucosal epithelium responds to intestinal pathogens through its secretion of inflammatory cytokines, chemokines, and antimicrobial peptides. Chemokines, such as IL-8 and IL-17, recruit neutrophils into the cecal mucosa to defend against the invasion of Salmonella, but induce excessive inflammation contributing to colitis. Some of the interleukins have anti-inflammatory effects, such as IL-10, while others have pro-inflammatory effects, such as IL-1β, IL-12/IL-23, IL-15, IL-18, and IL-22. Furthermore, some interleukins, such as IL-6 and IL-27, exhibit both pro- and anti-inflammatory functions and anti-microbial defenses. The majority of interleukins secreted by macrophages and lymphocytes contributes antimicrobial defense or protective effects, but IL-8 and IL-10 may promote systemic Salmonella infection. In this article, we review the interleukins involved in Salmonella infection in the literature.

scholarly journals Type I Interferon Signaling Is a Common Factor Driving Streptococcus pneumoniae and Influenza A Virus Shedding and Transmission

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Tonia Zangari ◽  
Mila B. Ortigoza ◽  
Kristen L. Lokken-Toyli ◽  
Jeffrey N. Weiser
Keyword(s):  
Streptococcus Pneumoniae ◽  
Respiratory Tract ◽  
Influenza A Virus ◽  
Influenza A ◽  
Common Factor ◽  
Type I ◽  
Upper Respiratory Tract ◽  
Content Type ◽  
Infant Mouse ◽  
Upper Respiratory

ABSTRACT The dynamics underlying respiratory contagion (the transmission of infectious agents from the airways) are poorly understood. We investigated host factors involved in the transmission of the leading respiratory pathogen Streptococcus pneumoniae. Using an infant mouse model, we examined whether S. pneumoniae triggers inflammatory pathways shared by influenza A virus (IAV) to promote nasal secretions and shedding from the upper respiratory tract to facilitate transit to new hosts. Here, we show that amplification of the type I interferon (IFN-I) response is a critical host factor in this process, as shedding and transmission by both IAV and S. pneumoniae were decreased in pups lacking the common IFN-I receptor (Ifnar1−/− mice). Additionally, providing exogenous recombinant IFN-I to S. pneumoniae-infected pups was sufficient to increase bacterial shedding. The expression of IFN-stimulated genes (ISGs) was upregulated in S. pneumoniae-infected wild-type (WT) but not Ifnar1−/− mice, including genes involved in mucin type O-glycan biosynthesis; this correlated with an increase in secretions in S. pneumoniae- and IAV-infected WT compared to Ifnar1−/− pups. S. pneumoniae stimulation of ISGs was largely dependent on its pore-forming toxin, pneumolysin, and coinfection with IAV and S. pneumoniae resulted in synergistic increases in ISG expression. We conclude that the induction of IFN-I signaling appears to be a common factor driving viral and bacterial respiratory contagion. IMPORTANCE Respiratory tract infections are a leading cause of childhood mortality and, globally, Streptococcus pneumoniae is the leading cause of mortality due to pneumonia. Transmission of S. pneumoniae primarily occurs through direct contact with respiratory secretions, although the host and bacterial factors underlying transmission are poorly understood. We examined transmission dynamics of S. pneumoniae in an infant mouse model and here show that S. pneumoniae colonization of the upper respiratory tract stimulates host inflammatory pathways commonly associated with viral infections. Amplification of this response was shown to be a critical host factor driving shedding and transmission of both S. pneumoniae and influenza A virus, with infection stimulating expression of a wide variety of genes, including those involved in the biosynthesis of mucin, a major component of respiratory secretions. Our findings suggest a mechanism facilitating S. pneumoniae contagion that is shared by viral infection.

scholarly journals Anterior Nares Diversity and Pathobionts Represent Sinus Microbiome in Chronic Rhinosinusitis

mSphere ◽  
2019 ◽  
Vol 4 (6) ◽  
Author(s):  
Ilke De Boeck ◽  
Stijn Wittouck ◽  
Katleen Martens ◽  
Jos Claes ◽  
Mark Jorissen ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Haemophilus Influenzae ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Sinus Surgery ◽  
Disease Development ◽  
Healthy Controls ◽  
Upper Respiratory Tract ◽  
Content Type ◽  
Upper Respiratory

ABSTRACT It is generally believed that the microbiome plays a role in the pathophysiology of chronic rhinosinusitis (CRS), though its exact contribution to disease development and severity remains unclear. Here, samples were collected from the anterior nares, nasopharynx, and maxillary and ethmoid sinuses of 190 CRS patients and from the anterior nares and nasopharynx of 100 controls. Microbial communities were analyzed by Illumina sequencing of the V4 region of 16S rRNA. The phenotype and patient characteristics were documented, and several serum inflammatory markers were measured. Our data indicate a rather strong continuity for the microbiome in the different upper respiratory tract (URT) niches in CRS patients, with the microbiome in the anterior nares being most similar to the sinus microbiome. Bacterial diversity was reduced in CRS patients without nasal polyps compared to that in the controls but not in CRS patients with nasal polyps. Statistically significant differences in the presence/absence or relative abundance of several taxa were found between the CRS patients and the healthy controls. Of these, Dolosigranulum pigrum was clearly more associated with URT samples from healthy subjects, while the Corynebacterium tuberculostearicum, Haemophilus influenzae/H. aegyptius, and Staphylococcus taxa were found to be potential pathobionts in CRS patients. However, CRS versus health as a predictor explained only 1 to 2% of the variance in the microbiome profiles in an adonis model. A history of functional endoscopic sinus surgery, age, and sex also showed a minor association. This study thus indicates that functional studies on the potential beneficial versus pathogenic activity of the different indicator taxa found here are needed to further understand the pathology of CRS and its different phenotypes. (This study has been registered at ClinicalTrials.gov under identifier NCT02933983.) IMPORTANCE There is a clear need to better understand the pathology and specific microbiome features in chronic rhinosinusitis patients, but little is known about the bacterial topography and continuity between the different niches of the upper respiratory tract. Our work showed that the anterior nares could be an important reservoir for potential sinus pathobionts. This has implications for the diagnosis, prevention, and treatment of CRS. In addition, we found a potential pathogenic role for the Corynebacterium tuberculostearicum, Haemophilus influenzae/H. aegyptius, and Staphylococcus taxa and a potential beneficial role for Dolosigranulum. Finally, a decreased microbiome diversity was observed in patients with chronic rhinosinusitis without nasal polyps compared to that in healthy controls but not in chronic rhinosinusitis patients with nasal polyps. This suggests a potential role for the microbiome in disease development or progression of mainly this phenotype.

scholarly journals Frequency of Owner-Reported Bacterial Infections in Pet Guinea Pigs

Animals ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 649 ◽  
Author(s):  
Shannon Roberts-Steel ◽  
James A. Oxley ◽  
Aisling Carroll ◽  
Alison P. Wills
Keyword(s):  
Guinea Pig ◽  
Bacterial Infection ◽  
Guinea Pigs ◽  
Bacterial Infections ◽  
Upper Respiratory Tract ◽  
Online Questionnaire ◽  
Gastrointestinal Infections ◽  
Husbandry Practices ◽  
Upper Respiratory ◽  
Tract Infections

Domestic guinea pigs suffer morbidity and mortality due to a range of bacterial infections amongst other causes. Microorganisms such as Bordetella bronchiseptica and Streptococcus pneumoniae are commonly implicated in respiratory disease; however, there is a lack of research surrounding the prevalence of these bacterial infections. The aim of this study was to investigate the frequency with which owners reported bacterial infections in pet guinea pigs and to assess owner knowledge of correct husbandry practices to inform prevention of the development of bacterial infections. An online questionnaire, consisting of 30 questions was promoted to guinea pig owners. Of all respondents (n = 524), 39.39% reported that their guinea pig(s) had been clinically diagnosed with a bacterial infection, with upper respiratory tract infections the most commonly reported (46.95%), followed by urinary tract (15.49%) and then gastrointestinal infections (11.73%). Owners demonstrated knowledge of correct husbandry practices and there was no significant effect (p = 0.475) of owner knowledge on having owned a guinea pig with a bacterial infection. Bacterial infections may be more common in guinea pigs than was previously thought. Further research is required to understand why bacterial infections are common in pet guinea pigs and to help owners to prevent and recognize these infections.

scholarly journals Increased Chain Length Promotes Pneumococcal Adherence and Colonization

2012 ◽  
Vol 80 (10) ◽  
pp. 3454-3459 ◽  
Author(s):  
Jesse L. Rodriguez ◽  
Ankur B. Dalia ◽  
Jeffrey N. Weiser
Keyword(s):  
Parental Strain ◽  
A549 Cells ◽  
Invasive Disease ◽  
Upper Respiratory Tract ◽  
Epithelial Surface ◽  
Content Type ◽  
Morphological Heterogeneity ◽  
Upper Respiratory

ABSTRACTStreptococcus pneumoniaeis a mucosal pathogen that grows in chains of variable lengths. Short-chain forms are less likely to activate complement, and as a consequence they evade opsonophagocytic clearance more effectively during invasive disease. When grown in human nasal airway surface fluid, pneumococci exhibited both short- and long-chain forms. Here, we determined whether longer chains provide an advantage during colonization when the organism is attached to the epithelial surface. Chain-forming mutants and the parental strain grown under conditions to promote chain formation showed increased adherence to human epithelial cells (A549 cells)in vitro. Additionally, adherence to A549 cells selected for longer chains within the wild-type strain.In vivoin a murine model of colonization, chain-forming mutants outcompeted the parental strain. Together, our results demonstrate that morphological heterogeneity in the pneumococcus may promote colonization of the upper respiratory tract by enhancing the ability of the organism to bind to the epithelial surface.

scholarly journals Upper Respiratory Tract Microbial Communities, Acute Otitis Media Pathogens, and Antibiotic Use in Healthy and Sick Children

2012 ◽  
Vol 78 (17) ◽  
pp. 6262-6270 ◽  
Author(s):  
Melinda M. Pettigrew ◽  
Alison S. Laufer ◽  
Janneane F. Gent ◽  
Yong Kong ◽  
Kristopher P. Fennie ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Microbial Communities ◽  
Otitis Media ◽  
Acute Otitis Media ◽  
Antibiotic Use ◽  
Healthy Children ◽  
Upper Respiratory Tract ◽  
Content Type ◽  
The Past ◽  
Upper Respiratory

ABSTRACTThe composition of the upper respiratory tract microbial community may influence the risk for colonization by the acute otitis media (AOM) pathogensStreptococcus pneumoniae,Haemophilus influenzae, andMoraxella catarrhalis. We used culture-independent methods to describe upper respiratory tract microbial communities in healthy children and children with upper respiratory tract infection with and without concurrent AOM. Nasal swabs and data were collected in a cross-sectional study of 240 children between 6 months and 3 years of age. Swabs were cultured forS. pneumoniae, and real-time PCR was used to identifyS. pneumoniae,H. influenzae, andM. catarrhalis. The V1-V2 16S rRNA gene regions were sequenced using 454 pyrosequencing. Microbial communities were described using a taxon-based approach. Colonization byS. pneumoniae,H. influenzae, andM. catarrhaliswas associated with lower levels of diversity in upper respiratory tract flora. We identified commensal taxa that were negatively associated with colonization by each AOM bacterial pathogen and with AOM. The balance of these relationships differed according to the colonizing AOM pathogen and history of antibiotic use. Children with antibiotic use in the past 6 months and a greater abundance of taxa, includingLactococcusandPropionibacterium, were less likely to have AOM than healthy children (odds ratio [OR], 0.46; 95% confidence interval [CI], 0.25 to 0.85). Children with no antibiotic use in the past 6 months, a low abundance ofStreptococcusandHaemophilus, and a high abundance ofCorynebacteriumandDolosigranulumwere less likely to have AOM (OR, 0.51; 95% CI, 0.31 to 0.83). An increased understanding of polymicrobial interactions will facilitate the development of effective AOM prevention strategies.

scholarly journals The cGAS/STING Pathway Detects Streptococcus pneumoniae but Appears Dispensable for Antipneumococcal Defense in Mice and Humans

2017 ◽  
Vol 86 (3) ◽  
Author(s):  
Juan Sebastian Ruiz-Moreno ◽  
Lutz Hamann ◽  
Lei Jin ◽  
Leif E. Sander ◽  
Monika Puzianowska-Kuznicka ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Type I ◽  
Upper Respiratory Tract ◽  
Content Type ◽  
Type I Ifns ◽  
Mouse Macrophages ◽  
Upper Respiratory ◽  
Sting Pathway ◽  
And Control ◽  
Wall Components

ABSTRACT Streptococcus pneumoniae is a frequent colonizer of the upper respiratory tract and a leading cause of bacterial pneumonia. The innate immune system senses pneumococcal cell wall components, toxin, and nucleic acids, which leads to production of inflammatory mediators to initiate and control antibacterial defense. Here, we show that the cGAS (cyclic GMP-AMP [cGAMP] synthase)-STING pathway mediates detection of pneumococcal DNA in mouse macrophages to primarily stimulate type I interferon (IFN) responses. Cells of human individuals carrying HAQ TMEM173 , which encodes a common hypomorphic variant of STING, were largely or partly defective in inducing type I IFNs and proinflammatory cytokines upon infection. Subsequent analyses, however, revealed that STING was dispensable for restricting S. pneumoniae during acute pneumonia in mice. Moreover, explorative analyses did not find differences in the allele frequency of HAQ TMEM173 in nonvaccinated pneumococcal pneumonia patients and healthy controls or an association of HAQ TMEM173 carriage with disease severity. Together, our results indicate that the cGAS/STING pathway senses S. pneumoniae but plays no major role in antipneumococcal immunity in mice and humans.

scholarly journals Serum β2-microglobulin may be a viral biomarker by analyzing children with upper respiratory tract infections and exanthem subitum: a retrospective study

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11109
Author(s):  
Xulong Cai ◽  
Qiaolan Xu ◽  
Chenrong Zhou ◽  
Tongjin Yin ◽  
Li Zhou
Keyword(s):  
Retrospective Study ◽  
Tract Infection ◽  
Respiratory Tract ◽  
Bacterial Infection ◽  
Respiratory Tract Infection ◽  
Upper Respiratory Tract Infection ◽  
Upper Respiratory Tract ◽  
Exanthem Subitum ◽  
Upper Respiratory ◽  
Tract Infections

Background Due to the lack of effective and feasible viral biomarkers to distinguish viral infection from bacterial infection, children often receive unnecessary antibiotic treatment. To identify serum β2-microglobulin that distinguishes bacterial upper respiratory tract infection from viral upper respiratory tract infection and exanthem subitum in children. Methods This retrospective study was conducted from January 1, 2019 to September 30, 2020 in Yancheng Third People’s Hospital. Children with upper respiratory tract infection and exanthem subitum were recruited. The concentration of serum β2-microglobulin in the viral and bacterial infection groups were statistically analyzed. Results A total of 291 children included 36 with bacterial upper respiratory tract infection (median age, 13 months; 44.4% female), 197 with viral upper respiratory tract infection (median age, 12 months; 43.7% female) and 58 with exanthem subitum (median age, 13 months; 37.9% female). When the concentration of β2-microglobulin was 2.4mg/L, the sensitivity to distinguish viral from bacterial upper respiratory tract infection was 81.2% (95% CI [75.1–86.4%]), and the specificity was 80.6% (95% CI [64.0–91.8]%). When the cutoff was 2.91 mg/L, the sensitivity of β2-microglobulin to distinguish exanthem subitum from bacterial upper respiratory tract infection was 94.8% (95% CI [85.6–98.9]%), and the specificity was 100% (95% CI [90.3–100]%). Conclusions Serum β2-microglobulin may be a significant biological indicator in children with upper respiratory tract infection and exanthem subitum.

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