Coeliac disease and invasive pneumococcal disease: a population-based cohort study.

Severe infections are recognized complications of coeliac disease (CD). In the present study we aimed to examine whether individuals with CD are at increased risk of invasive pneumococcal disease (IPD). To do so, we performed a population-based cohort study including 29 012 individuals with biopsy-proven CD identified through biopsy reports from all pathology departments in Sweden. Each individual with CD was matched with up to five controls (n = 144 257). IPD events were identified through regional and national microbiological databases, including the National Surveillance System for Infectious Diseases. We used Cox regression analyses to estimate hazard ratios (HRs) for diagnosed IPD. A total of 207 individuals had a record of IPD whereas 45/29 012 had CD (0·15%) and 162/144 257 were controls (0·11%). This corresponded to a 46% increased risk for IPD [HR 1·46, 95% confidence interval (CI) 1·05-2·03]. The risk estimate was similar after adjustment for socioeconomic status, educational level and comorbidities, but then failed to attain statistical significance (adjusted HR 1·40, 95% CI 0·99-1·97). Nonetheless, our study shows a trend towards an increased risk for IPD in CD patients. The findings support results seen in earlier research and taking that into consideration individuals with CD may be considered for pneumococcal vaccination.

Lung epithelium and myeloid cells cooperate to clear acute pneumococcal infection.

The Gram-positive bacterium Streptococcus pneumoniae causes life-threatening infections, especially among immunocompromised patients. The host's immune system senses S. pneumoniae via different families of pattern recognition receptors, in particular the Toll-like receptor (TLR) family that promotes immune cell activation. Yet, while single TLRs are dispensable for initiating inflammatory responses against S. pneumoniae, the central TLR adapter protein myeloid differentiation factor 88 (MyD88) is of vital importance, as MyD88-deficient mice succumb rapidly to infection. Since MyD88 is ubiquitously expressed in hematopoietic and non-hematopoietic cells, the extent to which MyD88 signaling is required in different cell types to control S. pneumoniae is unknown. Therefore, we used novel conditional knockin mice to investigate the necessity of MyD88 signaling in distinct lung-resident myeloid and epithelial cells for the initiation of a protective immune response against S. pneumoniae. Here, we show that MyD88 signaling in lysozyme M (LysM)- and CD11c-expressing myeloid cells, as well as in pulmonary epithelial cells, is critical to restore inflammatory cytokine and antimicrobial peptide production, leading to efficient neutrophil recruitment and enhanced bacterial clearance. Overall, we show a novel synergistic requirement of compartment-specific MyD88 signaling in S. pneumoniae immunity.

Oral bacterial community dynamics in paediatric patients with malignancies in relation to chemotherapy-related oral mucositis: a prospective study.

The role of oral bacteria in the development of chemotherapy-related oral mucositis has not been fully elucidated. This study aimed to investigate oral bacterial community diversity and dynamics in paediatric patients with malignancies in relation to the occurrence of oral mucositis. Patients with malignancies (n = 37) and reference individuals without known systemic disorders (n = 38) were recruited. For patients, oral bacterial samples were taken from mucosal surfaces both at the time of malignancy diagnosis and during chemotherapy. If oral mucositis occurred, samples were taken from the surface of the mucositis lesions. Oral mucosal bacterial samples were also taken from reference individuals. All samples were assessed using a 16S ribosomal RNA gene 454 pyrosequencing method. A lower microbial diversity (p < 0.01) and a higher intersubject variability (p < 0.001) were found in patients as compared with reference individuals. At the time of malignancy diagnosis (i.e. before chemotherapy) patients that later developed mucositis showed a higher microbial diversity (p < 0.05) and a higher intersubject variability (p < 0.001) compared with those without mucositis. The change of bacterial composition during chemotherapy was more pronounced in patients who later developed mucositis than those without mucositis (p < 0.01). In conclusion, we found a higher microbial diversity at the time of malignancy diagnosis in patients who later develop oral mucositis and that these patients had a more significant modification of the bacterial community by chemotherapy before the occurrence of mucositis. These findings may possibly be of clinical importance in developing better strategies for personalized preventive management.

Cloning, expression, purification, crystallization and preliminary X-ray analysis of the pilus-associated sortase C from Streptococcus pneumoniae.

The pilus-associated sortase C from Streptococcus pneumoniae (SrtC or Srt-2) acts as a polymerase for the pilus subunit proteins RrgA and RrgB. Here, the crystallization and preliminary X-ray diffraction analysis of three crystal forms of SrtC are reported. One crystal form belongs to space group P2(1)2(1)2(1), with unit-cell parameters a = 48.9, b = 96.9, c = 98.9 A, alpha = beta = gamma = 90 degrees . The other two crystal forms belong to space group P222, with unit-cell parameters a = 48.8, b = 97.2, c = 99.2 A, alpha = beta = gamma = 90 degrees and a = 48.6, b = 96.5, c = 98.8 A, alpha = beta = gamma = 90 degrees , respectively. Preliminary analysis indicates the presence of two molecules in the asymmetric unit of the crystal for all three forms.

RrgA is a pilus-associated adhesin in Streptococcus pneumoniae.

Adherence to host cells is important in microbial colonization of a mucosal surface, and Streptococcus pneumoniae adherence was significantly enhanced by expression of an extracellular pilus composed of three subunits, RrgA, RrgB and RrgC. We sought to determine which subunit(s) confers adherence. Bacteria deficient in RrgA are significantly less adherent than wild-type organisms, while overexpression of RrgA enhances adherence. Recombinant monomeric RrgA binds to respiratory cells, as does RrgC with less affinity, and pre-incubation of epithelial cells with RrgA reduces adherence of wild-type piliated pneumococci. Non-adherent RrgA-negative, RrgB- and RrgC-positive organisms produce pili, suggesting that pilus-mediated adherence is due to expression of RrgA, rather than the pilus backbone itself. In contrast, RrgA-positive strains with disrupted rrgB and rrgC genes exhibit wild-type adherence despite failure to produce pili by Western blot or immunoelectron microscopy. The density of bacteria colonizing the upper respiratory tract of mice inoculated with piliated RrgA-negative pneumococci was significantly less compared with wild-type; in contrast, non-piliated pneumococci expressing non-polymeric RrgA had similar numbers of bacteria in the nasopharynx as piliated wild-type bacteria. These data suggest that RrgA is central in pilus-mediated adherence and disease, even in the absence of polymeric pilus production.