Streptococcus pneumoniae is a leading cause of pneumonia, meningitis, and sepsis. Pneumococci can be divided into >90 serotypes that show differences in the pathogenicity and invasiveness. We tested the hypotheses that the innate immune inflammasome pathway is involved in fighting pneumococcal pneumonia and that some invasive pneumococcal types are not recognized by this pathway. We show that human and murine mononuclear cells responded to S. pneumoniae expressing hemolytic pneumolysin by producing IL-1β. This IL-1β production depended on the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. Some serotype 1, serotype 8, and serotype 7F bacteria, which have previously been associated with increased invasiveness and with production of toxins with reduced hemolytic activity, or bacterial mutants lacking pneumolysin did not stimulate notable IL-1β production. We further found that NLRP3 was beneficial for mice during pneumonia caused by pneumococci expressing hemolytic pneumolysin and was involved in cytokine production and maintenance of the pulmonary microvascular barrier. Overall, the inflammasome pathway is protective in pneumonia caused by pneumococci expressing hemolytic toxin but is not activated by clinically important pneumococcal sequence types causing invasive disease. The study indicates that a virulence factor polymorphism may substantially affect the recognition of bacteria by the innate immune system.

SummaryStreptococcus pneumoniae is both a frequent colonizer of the upper respiratory tract and a leading cause of life-threatening infections such as pneumonia, meningitis and sepsis. The innate immune system is critical for the control of colonization and for defence during invasive disease. Initially, pneumococci are recognized by different sensors of the innate immune system called pattern recognition receptors (PRRs), which control most subsequent host defence pathways. These PRRs include the transmembrane Toll-like receptors (TLRs) as well as the cytosolic NOD-like receptors (NLRs) and DNA sensors. Recognition of S. pneumoniae by members of these PRR families regulates the production of inflammatory mediators that orchestrate the following immune response of infected as well as neighbouring non-infected cells, stimulates the recruitment of immune cells such as neutrophils and macrophages, and shapes the adaptive immunity. This review summarizes the current knowledge of the function of different PRRs in S. pneumoniae infection.

Streptococcus pneumoniae is the leading cause of community-acquired pneumonia. In this study, we examine an innate immune recognition pathway that senses pneumococcal infection, triggers type I IFN production, and regulates RANTES production. We found that human and murine alveolar macrophages as well as murine bone marrow macrophages, but not alveolar epithelial cells, produced type I IFNs upon infection with S. pneumoniae. This response was dependent on the pore-forming toxin pneumolysin and appeared to be mediated by a cytosolic DNA-sensing pathway involving the adapter molecule STING and the transcription factor IFN regulatory factor 3. Indeed, DNA was present in the cytosol during pneumococcal infection as indicated by the activation of the AIM2 inflammasome, which is known to sense microbial DNA. Type I IFNs produced by S. pneumoniae-infected macrophages positively regulated gene expression and RANTES production in macrophages and cocultured alveolar epithelial cells in vitro. Moreover, type I IFNs controlled RANTES production during pneumococcal pneumonia in vivo. In conclusion, we identified an immune sensing pathway detecting S. pneumoniae that triggers a type I IFN response and positively regulates RANTES production.

Background Due to limited therapeutic options, vancomycin-resistant Enterococcus faecium (VREF) is of great clinical significance. Recently, rising proportions of vancomycin resistance in enterococcal infections have been reported worldwide. This study aims to describe current epidemiological trends of VREF in German hospitals and to identify factors that are associated with an increased likelihood of vancomycin resistance in clinical E. faecium isolates. Methods 2012 to 2017 data from routine vancomycin susceptibility testing of 35,906 clinical E. faecium isolates from 148 hospitals were analysed using data from the German Antimicrobial Resistance Surveillance System. Descriptive statistical analyses and uni- and multivariable regression analyses were performed to investigate the impact of variables, such as year of sampling, age and region, on vancomycin resistance in clinical E. faecium isolates. Results From 2014 onwards the proportions of clinical E. faecium isolates exhibiting resistance to vancomycin increased from 11.2% (95% confidence interval [CI] 9.4–13.3%) to 26.1% (95% CI 23.1–29.4%) in 2017. The rise of VREF proportions is primarily observed in the southern regions of Germany, whereas northern regions do not show a major increase. In the Southwest and Southeast, VREF proportions increased from 10.8% (95% CI 6.9–16.5%) and 3.8% (95% CI 3.0–11.5%) in 2014 to 36.7% (95% CI 32.9–40.8%) and 36.8% (95% CI 29.2–44.7%) in 2017, respectively. VREF proportions were considerably higher in isolates from patients aged 40–59 years compared to younger patients. Further regression analyses show that in relation to secondary care hospitals, E. faecium samples collected in specialist care hospitals and prevention and rehabilitation care centres are more likely to be vancomycin-resistant (odds ratios: 2.4 [95% CI 1.2–4.6] and 2.4 [95% CI 1.9–3.0], respectively). No differences in VREF proportions were found between female and male patients as well as between different clinical specimens. Conclusion The proportion of VREF is increasing in German hospitals, particularly in southern regions in Germany. Increased efforts in infection control and antibiotic stewardship activities accounting for local resistance patterns are necessary to combat the spread of VREF in Germany. Electronic supplementary material The online version of this article (10.1186/s13756-019-0594-3) contains supplementary material, which is available to authorized users.

By 22 June 2022, 521 cases of monkeypox were notified in Germany. The median age was 38 years (IQR: 32–44); all cases were men. In Berlin, where 69% of all cases occurred, almost all were men who have sex with men. Monkeypox virus likely circulated unrecognised in Berlin before early May. Since mid-May, we observed a shift from travel-associated infections to mainly autochthonous transmission that predominantly took place in Berlin, often in association with visits to clubs and parties.