Effect of a pneumococcal whole cell vaccine on influenza A-induced pneumococcal otitis media in infant mice.

The pneumococcus remains a common cause of otitis media (OM) despite the widespread introduction of pneumococcal conjugate vaccines. In mice, a pneumococcal whole cell vaccine (WCV) induces serotype-independent protection against pneumococcal colonisation and invasive disease via T17- and antibody-mediated immunity, respectively. We investigated the effect of WCV on influenza A-induced pneumococcal OM in an infant mouse model.

Increased autoimmune diabetes in pIgR-deficient NOD mice is due to a "Hitchhiking" interval that refines the genetic effect of Idd5.4.

Selective breeding to introduce a gene mutation from one mouse strain onto the genetic background of another strain invariably produces "hitchhiking" (i.e. flanking) genomic intervals, which may independently affect a disease trait of interest.

Analysis of Salmonella enterica serovar Typhimurium variable-number tandem-repeat data for public health investigation based on measured mutation rates and whole-genome sequence comparisons.

Variable-number tandem repeats (VNTRs) mutate rapidly and can be useful markers for genotyping. While multilocus VNTR analysis (MLVA) is increasingly used in the detection and investigation of food-borne outbreaks caused by Salmonella enterica serovar Typhimurium (S. Typhimurium) and other bacterial pathogens, MLVA data analysis usually relies on simple clustering approaches that may lead to incorrect interpretations.

Congenic mice reveal genetic epistasis and overlapping disease loci for autoimmune diabetes and listeriosis.

The nonobese diabetic (NOD) mouse strain serves as a genomic standard for assessing how allelic variation for insulin-dependent diabetes (Idd) loci affects the development of autoimmune diabetes. We previously demonstrated that C57BL/6 (B6) mice harbor a more diabetogenic allele than NOD mice for the Idd14 locus when introduced onto the NOD genetic background. New congenic NOD mouse strains, harboring smaller B6-derived intervals on chromosome 13, now localize Idd14 to an ~18-Mb interval and reveal a new locus, Idd31.

Evaluation of intra- and extra-epithelial secretory IgA in chlamydial infections.

Immunoglobulin A is an important mucosal antibody that can neutralize mucosal pathogens by either preventing attachment to epithelia (immune exclusion) or alternatively inhibit intra-epithelial replication following transcytosis by the polymeric immunoglobulin receptor (pIgR). Chlamydia trachomatis is a major human pathogen that initially targets the endocervical or urethral epithelium in women and men, respectively. As both tissues contain abundant secretory IgA (SIgA) we assessed the protection afforded by IgA targeting different chlamydial antigens expressed during the extra- and intra-epithelial stages of infection.

Antibodies mediate formation of neutrophil extracellular traps in the middle ear and facilitate secondary pneumococcal otitis media.

Otitis media (OM) (a middle ear infection) is a common childhood illness that can leave some children with permanent hearing loss. OM can arise following infection with a variety of different pathogens, including a coinfection with influenza A virus (IAV) and Streptococcus pneumoniae (the pneumococcus). We and others have demonstrated that coinfection with IAV facilitates the replication of pneumococci in the middle ear.

Contribution of secretory antibodies to intestinal mucosal immunity against Helicobacter pylori.

The natural immune response to Helicobacter pylori neither clears infection nor prevents reinfection. However, the ability of secretory antibodies to influence the course of H. pylori infection has not been determined.

Systemic infection of Mice with Listeria monocytogenes to characterize host immune responses.

Listeria monocytogenes is a Gram-positive facultative intracellular bacterium that is widely used to characterize bacterial pathogenesis and host immunity. Here, we describe a set of basic methods and techniques to infect mice with L. monocytogenes, measure bacterial load in tissues, and analyze immune cell subsets responding to infection in the spleen and liver.

Influenza A virus induced bacterial otitis media is independent of virus tropism for α2,6-linked sialic acid.

Background: Otitis media (OM) affects ≥80% of children before the age of three. OM can arise following co-infection with influenza A virus (IAV) and the bacterium Streptococcus pneumoniae. We have previously shown that H3 IAV strains (such as Udorn/72) induced a higher rate of bacterial OM than H1 strains (such as PR8/34).

Increased antigen specific T cell numbers in the absence of altered migration or division rates as a result of mucosal cholera toxin administration.

Cholera toxin (CT) is a mucosal adjuvant capable of inducing strong immune responses to co-administered antigens following oral or intranasal immunization of mice. To date, the direct effect of CT on antigen-specific CD4(+) T cell migration and proliferation profiles in vivo is not well characterized. In this study, the effect of CT on the migration pattern and proliferative responses of adoptively transferred, CD4(+) TCR transgenic T cells in orally or intranasally vaccinated mice, was analyzed by flow cytometry.

Influenza-induced inflammation drives pneumococcal otitis media.

Influenza A virus (IAV) predisposes individuals to secondary infections with the bacterium Streptococcus pneumoniae (the pneumococcus). Infections may manifest as pneumonia, sepsis, meningitis, or otitis media (OM). It remains controversial as to whether secondary pneumococcal disease is due to the induction of an aberrant immune response or IAV-induced immunosuppression.

Increased nasopharyngeal bacterial titers and local inflammation facilitate transmission of Streptococcus pneumoniae.

Unlabelled: The transmission of the bacterium Streptococcus pneumoniae (the pneumococcus) marks the first step toward disease development. To date, our ability to prevent pneumococcal transmission has been limited by our lack of understanding regarding the factors which influence the spread of this pathogen. We have previously developed an infant mouse model of pneumococcal transmission which was strictly dependent on influenza A virus (IAV) coinfection of both the experimentally colonized "index mice" and the naive cohoused "contact mice.

NLRC4 inflammasomes in dendritic cells regulate noncognate effector function by memory CD8⁺ T cells.

Memory T cells exert antigen-independent effector functions, but how these responses are regulated is unclear. We discovered an in vivo link between flagellin-induced NLRC4 inflammasome activation in splenic dendritic cells (DCs) and host protective interferon-γ (IFN-γ) secretion by noncognate memory CD8(+) T cells, which could be activated by Salmonella enterica serovar Typhimurium, Yersinia pseudotuberculosis and Pseudomonas aeruginosa. We show that CD8α(+) DCs were particularly efficient at sensing bacterial flagellin through NLRC4 inflammasomes.

Influenza virus induces bacterial and nonbacterial otitis media.

Otitis media (OM) is one of the most common childhood diseases. OM can arise when a viral infection enables bacteria to disseminate from the nasopharynx to the middle ear. Here, we provide the first infant murine model for disease.

MrkH, a novel c-di-GMP-dependent transcriptional activator, controls Klebsiella pneumoniae biofilm formation by regulating type 3 fimbriae expression.

Klebsiella pneumoniae causes significant morbidity and mortality worldwide, particularly amongst hospitalized individuals. The principle mechanism for pathogenesis in hospital environments involves the formation of biofilms, primarily on implanted medical devices. In this study, we constructed a transposon mutant library in a clinical isolate, K.

Using bioluminescent imaging to investigate synergism between Streptococcus pneumoniae and influenza A virus in infant mice.

During the 1918 influenza virus pandemic, which killed approximately 50 million people worldwide, the majority of fatalities were not the result of infection with influenza virus alone. Instead, most individuals are thought to have succumbed to a secondary bacterial infection, predominately caused by the bacterium Streptococcus pneumoniae (the pneumococcus). The synergistic relationship between infections caused by influenza virus and the pneumococcus has subsequently been observed during the 1957 Asian influenza virus pandemic, as well as during seasonal outbreaks of the virus (reviewed in (1, 2)).

Local recall responses in the stomach involving reduced regulation and expanded help mediate vaccine-induced protection against Helicobacter pylori in mice.

Helicobacter pylori is recognised as the chief cause of chronic gastritis, ulcers and gastric cancer in humans. With increased incidence of treatment failure and antibiotic resistance, development of prophylactic or therapeutic vaccination is a desirable alternative. Although the results of vaccination studies in animal models have been promising, studies in human volunteers have revealed problems such as 'post-immunisation gastritis' and comparatively poor responses to vaccine antigens.

The role of secretory antibodies in infection immunity.

The mucosal secretory immune system provides an important primary defence against disease, as studies of humans with mucosal humoral immunodeficiencies suggest that the absence of secretory immunoglobulin A leads to an increase in mucosal infections. However, the infection risks posed do not seem to provide the evolutionary drive to retain constitutive secretion of often 'hard won' protein, suggesting that secretory antibodies may have some other important function (or functions). This Review examines the evidence that secretory antibodies provide an important defence against infection in specific animal models and explores complementary explanations for the evolution of the secretory immune system.

The multi-copper-ion oxidase CueO of Salmonella enterica serovar Typhimurium is required for systemic virulence.

Salmonella enterica serovar Typhimurium possesses a multi-copper-ion oxidase (multicopper oxidase), CueO (also known as CuiD), a periplasmic enzyme known to be required for resistance to copper ions. CueO from S. Typhimurium was expressed as a recombinant protein in Escherichia coli, and the purified protein exhibited a high cuprous oxidase activity.

Different bacterial pathogens, different strategies, yet the aim is the same: evasion of intestinal dendritic cell recognition.

Given the central role of intestinal dendritic cells (DCs) in the regulation of gut immune responses, it is not surprising that several bacterial pathogens have evolved strategies to prevent or bypass recognition by DCs. In this article, we will review recent findings on the interaction between intestinal DCs and prototypical bacterial pathogens, such as Salmonella, Yersinia, or Helicobacter. We will discuss the different approaches with which these pathogens seek to evade DC recognition and subsequent T cell activation.

Influenza A virus facilitates Streptococcus pneumoniae transmission and disease.

Streptococcus pneumoniae (the pneumococcus) kills approximately 1.6 million people annually. Pneumococcal infections predominantly manifest as pneumonia, sepsis, meningitis, and otitis media.

The major surface-associated saccharides of Klebsiella pneumoniae contribute to host cell association.

Analysing the pathogenic mechanisms of a bacterium requires an understanding of the composition of the bacterial cell surface. The bacterial surface provides the first barrier against innate immune mechanisms as well as mediating attachment to cells/surfaces to resist clearance. We utilised a series of Klebsiella pneumoniae mutants in which the two major polysaccharide layers, capsule and lipopolysaccharide (LPS), were absent or truncated, to investigate the ability of these layers to protect against innate immune mechanisms and to associate with eukaryotic cells.

Impact of prior immunological exposure on vaccine delivery by Salmonella enterica serovar Typhimurium.

Recombinant Salmonella have been employed as vaccine vectors to deliver DNA and protein vaccines of viral, bacterial and parasitic origin. However, the effectiveness of Salmonella delivery may be hampered by prior immunological exposure to Salmonella. We investigated the effects of prior exposure to the Salmonella typhimurium aroAD strain BRD509 on its ability to deliver the non-toxic C fragment of tetanus toxin (TT).

Targeting subcapsular antigens for prevention of Klebsiella pneumoniae infections.

Vaccination strategies against Klebsiella pneumoniae have largely focussed on the polysaccharide capsule. However, the large number and high prevalence of individual capsular serotypes limits the widespread applicability of capsule-based vaccines. This study establishes that immunization with purified LPS can protect mice against lethal challenge with K.

Macrophages are mediators of gastritis in acute Helicobacter pylori infection in C57BL/6 mice.

Helicobacter pylori is the etiological agent of human chronic gastritis, a condition seen as a precursor to the development of gastrointestinal ulcers or gastric cancer. This study utilized the murine model of chronic H. pylori infection to characterize the role of macrophages in the induction of specific immune responses and gastritis and in the control of the bacterial burden following H.