Serotype 1 and 8 Pneumococci Evade Sensing by Inflammasomes in Human Lung Tissue

Fatykhova, Diana; Rabes, Anne; Machnik, Christoph; Guruprasad, Kunchur; Pache, Florence; Berg, Johanna; Toennies, Mario; Bauer, Torsten T.; Schneider, Paul; Schimek, M; Eggeling, Stephan; Mitchell, Timothy J.; Mitchell, Andrea M.; Hilker, Rolf; Hain, Torsten; Suttorp, Norbert; Hippenstiel, Stefan; Hocke, Andreas C.; Opitz, Bastian

doi:10.1371/journal.pone.0137108

Cited by 36 publications

(39 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, each cytokine, upregulated in response to the IL-37-induced modulation of the immune response, might be specifically involved in exacerbating disease pathology. The downregulation of IL-1β, which has been shown to be required for protective immunity against respiratory infections with S. pneumoniae , may aggravate the pathogen ability to invade sterile compartments where it can continue multiplication without being eliminated [45,46] . Moreover, the elevated levels of IL-1β, which we observed later in infected IL-37tg mice, have the potential to aggravate tissue damage [13] .…”

Section: Discussionmentioning

confidence: 99%

IL-37 Causes Excessive Inflammation and Tissue Damage in Murine Pneumococcal Pneumonia

et al. 2017

View full text Add to dashboard Cite

Streptococcus pneumoniae infections can lead to severe complications with excessive immune activation and tissue damage. Interleukin-37 (IL-37) has gained importance as a suppressor of innate and acquired immunity, and its effects have been therapeutic as they prevent tissue damage in autoimmune and inflammatory diseases. By using RAW macrophages, stably transfected with human IL-37, we showed a 70% decrease in the cytokine levels of IL-6, TNF-α, and IL-1β, and a 2.2-fold reduction of the intracellular killing capacity of internalized pneumococci in response to pneumococcal infection. In a murine model of infection with S. pneumoniae, using mice transgenic for human IL-37b (IL-37tg), we observed an initial decrease in cytokine expression of IL-6, TNF-α, and IL-1β in the lungs, followed by a late-phase enhancement of pneumococcal burden and subsequent increase of proinflammatory cytokine levels. Additionally, a marked increase in recruitment of alveolar macrophages and neutrophils was noted, while TRAIL mRNA was reduced 3-fold in lungs of IL-37tg mice, resulting in necrotizing pneumonia with augmented death of infiltrating neutrophils, enhanced bacteremic spread, and increased mortality. In conclusion, we have identified that IL-37 modulates several core components of a successful inflammatory response to pneumococcal pneumonia, which lead to increased inflammation, tissue damage, and mortality.

show abstract

Section: Discussionmentioning

confidence: 99%

IL-37 Causes Excessive Inflammation and Tissue Damage in Murine Pneumococcal Pneumonia

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The earlier presence of surfactant in female neonatal lungs helps open the small airways and may contribute to their higher airflow rate observed [50]. Evidence from human studies suggests that male infants are more susceptible to lung infection, with greater associated morbidity and mortality than female infants, but the reverse is applied in children and adolescents [47,51,52]. Regarding respiratory tract infections (RTIs), women are more 3.…”

Section: Gender Differences In Community-acquired Pneumoniamentioning

confidence: 99%

“…Studies using depletion of alveolar macrophages have demonstrated that these contribute largely to the stimulation of pro-inflammatory cytokines, such as IL-6 and TNFα [48]. Moreover, interleukin-1β (IL-1β) is induced only by strains containing the cholesterol-dependent cytolysin, pneumolysin (PLY), a major virulence factor of pneumococci infection [51]. In addition, the levels of tolllike receptor 2 (TLR2) and toll-like receptor 4 (TLR4) increase after S. pneumoniae infection in the Crl:CD1 mouse strain [96].…”

Section: Strain Differences and Associated Mechanismsmentioning

confidence: 99%

Understanding the Intersection of Environmental Pollution, Pneumonia, and Inflammation: Does Gender Play a Role?

Silveyra¹,

Fuentes²,

Rivera³

2017

Contemporary Topics of Pneumonia

View full text Add to dashboard Cite

Accumulating evidence indicates that exposure to air pollution is associated with increased mortality from respiratory disease. Exposure to ambient pollutants, such as ozone, particulate matter, sulfur dioxide, nitrogen dioxide, and other agents has been associated with decrease in lung function and immunity, and with increased rates of hospitalization for lung disease, including pneumonia. Furthermore, sex differences in frequency and severity of pulmonary disease and infection have been reported, suggesting a role of sex hormones in mediating these differences. Pneumonia, which is commonly caused by bacterial infection and subsequent lung inflammation leading to hospitalization and death, occurs at different rates in men and women. In this context, male and female hormones can have direct effects on the immunity system by binding to receptors in immune cells, and these responses can be modulated by environmental exposures. This chapter summarizes clinical, animal, and epidemiological studies linking exposure to air pollution and pneumonia in both males and females. Understanding sex-specific mechanisms in pneumonia pathogenesis and environmental responses can help in the development of more effective therapeutics and treatment options to reduce negative health outcomes in men and women.

show abstract

“…The ex vivo infection of human lungs with pneumococci induces the expression of immunomodulatory molecules such as tumor necrosis factor α (TNFα), interleukin-1β (IL-1β), granulocyte-macrophage colony-stimulating factor, plateletderived growth factor (PDGF), IL-6, IL-8, IL-10, IL-15, IL-17, or prostaglandin-E 2 (PGE 2 ; Fatykhova et al 2015;Szymanski et al 2012;Xu et al 2008). Experiments performed with the clodronate-induced depletion of alveolar lung macrophages (AM) indicated that these cells might, in particular, contribute to the induction of IL-6 and TNFα (Xu et al 2008).…”

Section: Streptococcus Pneumoniaementioning

confidence: 99%

“…Experiments performed with the clodronate-induced depletion of alveolar lung macrophages (AM) indicated that these cells might, in particular, contribute to the induction of IL-6 and TNFα (Xu et al 2008). Fatykhova et al (2015) involved the use of various clinical isolates to investigate their capacity to induce the potent pro-inflammatory cytokine IL-1β. These clinical strains differed in the expression of the cholesterol-dependent cytolysin pneumolysin (PLY), a major virulence factor of pneumococci (Kadioglu et al 2008): Whereas serotypes 2, 3, 6B and 9N pneumococci express fully hemolytic PLY, serotype 1 and 8 strains express non-hemolytic PLY (Fatykhova et al 2015).…”

Section: Streptococcus Pneumoniaementioning

confidence: 99%

Human lung ex vivo infection models

2016

Self Cite

View full text Add to dashboard Cite

Pneumonia is counted among the leading causes of death worldwide. Viruses, bacteria and pathogen-related molecules interact with cells present in the human alveolus by numerous, yet poorly understood ways. Traditional cell culture models little reflect the cellular composition, matrix complexity and three-dimensional architecture of the human lung. Integrative animal models suffer from species differences, which are of particular importance for the investigation of zoonotic lung diseases. The use of cultured ex vivo infected human lung tissue may overcome some of these limitations and complement traditional models. The present review gives an overview of common bacterial lung infections, such as pneumococcal infection and of widely neglected pathogens modeled in ex vivo infected lung tissue. The role of ex vivo infected lung tissue for the investigation of emerging viral zoonosis including influenza A virus and Middle East respiratory syndrome coronavirus is discussed. Finally, further directions for the elaboration of such models are revealed. Overall, the introduced models represent meaningful and robust methods to investigate principles of pathogen-host interaction in original human lung tissue.

show abstract

Serotype 1 and 8 Pneumococci Evade Sensing by Inflammasomes in Human Lung Tissue

Cited by 36 publications

References 54 publications

IL-37 Causes Excessive Inflammation and Tissue Damage in Murine Pneumococcal Pneumonia

IL-37 Causes Excessive Inflammation and Tissue Damage in Murine Pneumococcal Pneumonia

Understanding the Intersection of Environmental Pollution, Pneumonia, and Inflammation: Does Gender Play a Role?

Human lung ex vivo infection models

Contact Info

Product

Resources

About