BASIC AND TRANSLATIONAL LIVER the WDF and given injections of anti-IL11 or anti-IL11RA, as well as from Il11ra1-/mice fed WDF, had lower serum levels of lipids and glucose than mice not injected with antibody or with disruption of Il11ra1. CONCLUSIONS: Neutralizing antibodies that block IL11 signaling reduce fibrosis, steatosis, hepatocyte death, inflammation and hyperglycemia in mice with dietinduced steatohepatitis. These antibodies also improve the cardiometabolic profile of mice and might be developed for the treatment of NASH.

Streptococcus pneumoniae is a major cause of pneumonia, sepsis and meningitis. The pore-forming toxin pneumolysin is a key virulence factor of S. pneumoniae, which can be sensed by the NLRP3 inflammasome. Among the over 90 serotypes, serotype 1 pneumococci (particularly MLST306) have emerged across the globe as a major cause of invasive disease. The cause for its particularity is, however, incompletely understood. We therefore examined pneumococcal infection in human cells and a human lung organ culture system mimicking infection of the lower respiratory tract. We demonstrate that different pneumococcal serotypes differentially activate inflammasome-dependent IL-1β production in human lung tissue and cells. Whereas serotype 2, 3, 6B, 9N pneumococci expressing fully haemolytic pneumolysins activate NLRP3 inflammasome-dependent responses, serotype 1 and 8 strains expressing non-haemolytic toxins are poor activators of IL-1β production. Accordingly, purified haemolytic pneumolysin but not serotype 1-associated non-haemolytic toxin activates strong IL-1β production in human lungs. Our data suggest that the evasion of inflammasome-dependent innate immune responses by serotype 1 pneumococci might contribute to their ability to cause invasive diseases in humans.

The innate immune system employs C-type lectin receptors (CLRs) to recognize carbohydrate structures on pathogens and self-antigens. The Macrophage-inducible C-type lectin (Mincle) is a FcRγ-coupled CLR that was shown to bind to mycobacterial cord factor as well as certain fungal species. However, since CLR functions during bacterial infections have not yet been investigated thoroughly, we aimed to examine their function in Streptococcus pneumonia infection. Binding studies using a library of recombinantly expressed CLR-Fc fusion proteins indicated a specific, Ca2+-dependent, and serotype-specific binding of Mincle to S. pneumonia. Subsequent experiments with different Mincle-expressing cells as well as Mincle-deficient mice, however, revealed a limited role of this receptor in bacterial phagocytosis, neutrophil-mediated killing, cytokine production, and antibacterial immune response during pneumonia. Collectively, our results indicate that Mincle is able to recognize S. pneumonia but is not required for the anti-pneumococcal innate immune response.

Streptococcus pneumoniae frequently colonizes the upper respiratory tract of healthy individuals, but also commonly causes severe invasive infections such as community-acquired pneumonia and meningitis. One of the key virulence factors of pneumococci is the pore-forming toxin pneumolysin which stimulates cell death and is involved in the evasion of some defense mechanisms. The immune system, however, employs different inflammasomes to sense pneumolysin-induced pore formation, cellular membrane damage, and/or subsequent leakage of bacterial nucleic acid into the host cell cytosol. Canonical inflammasomes are cytosolic multiprotein complexes consisting of a receptor molecule such as NLRP3 or AIM2, the adapter ASC, and caspase-1. NLRP3 and AIM2 inflammasomes mediate cell death and production of important IL-1 family cytokines to recruit leukocytes and defend against S. pneumoniae. Here, we review recent evidence that highlights inflammasomes as critical sensors of S. pneumoniae-induced cellular perturbations, summarize their role in pneumococcal infections, and discuss potential evasion strategies of some emerging pneumococcal strains.

Infection with the intravascular diecious trematode Schistosoma spp. remains a serious tropical disease and public health problem in the developing world, affecting over 258 million people worldwide. During chronic Schistosoma mansoni infection, complex immune responses to tissue-entrapped parasite eggs provoke granulomatous inflammation which leads to serious damage of the liver and intestine. The suppression of protective host immune mechanisms by helminths promotes parasite survival and benefits the host by reducing tissue damage. However, immune-suppressive cytokines may reduce vaccine-induced immune responses. By combining a single-sex infection system with a murine air pouch model, we were able to demonstrate that male and female schistosomes play opposing roles in modulating the host’s immune response. Female schistosomes suppress early innate immune responses to invading cercariae in the skin and upregulate anergy-associated genes. In contrast, male schistosomes trigger strong innate immune reactions which lead to a reduction in worm and egg burden in the liver. Our data suggest that the female worm is a neglected player in the dampening of the host’s immune defense system and is therefore a promising target for new immune modulatory therapies.

In recent decades, biofilm-associated infections have become a major problem in many medical fields, leading to a high burden on patients and enormous costs for the healthcare system. Microbial infestations are caused by opportunistic pathogens which often enter the incision already during implantation. In the subsequently formed biofilm bacteria are protected from the hosts immune system and antibiotic action. Therefore, the development of modified, anti-microbial implant materials displays an indispensable task. Thermoplastic polyurethane (TPU) represents the state-of-the-art material in implant manufacturing. Due to the constantly growing areas of application and the associated necessary adjustments, the optimization of these materials is essential. In the present study, modified liquid silicone rubber (LSR) surfaces were compared with two of the most commonly used TPUs in terms of bacterial colonization and biofilm formation. The tests were conducted with the clinically relevant bacterial strains Staphylococcus aureus and Staphylococcus epidermidis. Crystal violet staining and scanning electron microscopy showed reduced adhesion of bacteria and thus biofilm formation on these new materials, suggesting that the investigated materials are promising candidates for implant manufacturing.

As part of the parasite's excretory/secretory system, extracellular vesicles (EVs) represent a potent communication tool of schistosomes with their human host to strike the balance between their own survival in a hostile immunological environment and a minimal damage to the host tissue. Their cargo consists of functional proteins, lipids, and nucleic acids that facilitate biological processes like migration, nutrient acquisition, or reproduction. The most important impact of the vesicle-mediated communication, however, is the promotion of the parasite survival via mimicking host protein function and directly or indirectly modulating the immune response of the host. Overcoming this shield of immunological adaption in the schistosome-host relation is the aim of current research activities in this field and crucial for the development of a reliable anti-schistosomal therapy. Not least because of their prospective use in clinical applications, research on EVs is now a rapidly expanding field. We herein focus on the current state of knowledge of vesicle-based communication of schistosomes and discussing the role of EVs in facilitating biological processes and immune modulatory properties of EVs considering the different life stages of the parasite.

Schistosomiasis is one of the most devastating parasitic disease in the world. Schistosoma spp. survive for decades within the vasculature of their human hosts. They have evolved a vast array of mechanisms to avoid the immune reaction of the host. Due to their sexual dimorphism, with the female worm lying within the gynecophoric canal of the male worm, it is the male that is exposed to the immediate environment and the soluble parts of the host’s immune response. To understand how the worms are so successful in fending off the immune attacks of the host, comparative analyses of both worm sexes in human serum (with or without Praziquantel) were performed using scanning electron microscopy, transmission electron microscopy, and immunohistochemistry. Further, gene expression analyses of tegument-specific genes were performed. Following the incubation in human serum, males and females out of pairs show morphological changes such as an altered structure of the pits below the surface and an increased number of pits per area. In addition, female schistosomes presented a marked tuft-like repulsion of their opsonized surface. The observed resistance of females to Praziquantel seemed to depend on active proteins in the human serum. Moreover, different expression profiles of tegument-specific genes indicate different functions of female_single and male_single teguments in response to human serum. Our results indicate that female schistosomes developed different evasion strategies toward the host’s immune system in comparison to males that might lead to more robustness and has to be taken into account for the development of new anti-schistosomal drugs.