Platelets, cell fragments traditionally thought of as important only for hemostasis, substantially and dynamically contribute to the immune system’s response to infection. In addition, there is increasing evidence that externally active platelet entities, including platelet granules and platelet extracellular vesicles (PEVs), play a role not only in hemostasis, but also in inflammatory actions previously ascribed to platelets themselves. Given the functions of platelets and PEVs during inflammation and infection, their role in sepsis is being investigated. Sepsis is a condition marked by the dysregulation of the body’s normal activation of the immune system in response to a pathogen. The mechanisms for controlling infection locally become detrimental to the host if they are applied systemically. Similar to cells traditionally ascribed to the immune system, including neutrophils, lymphocytes, and macrophages, platelets are instrumental in helping a host clear an infection, but are also implicated in the uncontrolled amplification of the immune response that leads to sepsis. Clearly, the function of platelets is more complicated than its simple structure and primary role in hemostasis initially suggest. This review provides an overview of platelet and platelet extracellular vesicle structure and function, highlighting the complex role platelets and PEVs play in the body in the context of infection and sepsis.

PurposeEnd-organ apoptosis is well-described in progressive sepsis and Multiple Organ Dysfunction Syndrome (MODS), especially where platelets accumulate (e.g. spleen and lung). We previously reported an acute sepsis-induced cytotoxic platelet phenotype expressing serine protease granzyme B. We now aim to define the site(s) of and mechanism(s) by which platelet granzyme B induces end-organ apoptosis in sepsis.MethodsEnd-organ apoptosis in murine sepsis (i.e. polymicrobial peritonitis) was analyzed by immunohistochemistry. Platelet cytotoxicity was measured by flow cytometry following 90 minute ex vivo co-incubation with healthy murine splenocytes. Sepsis progression was measured via validated preclinical murine sepsis score.Measurements and Main ResultsThere was evident apoptosis in spleen, lung, and kidney sections from septic wild type mice. In contrast, there was a lack of TUNEL staining in spleens and lungs from septic granzyme B null mice and these mice survived longer following induction of sepsis than wild type mice. In co-incubation experiments, physical separation of septic platelets from splenocytes by a semi-permeable membrane reduced splenocyte apoptosis to a rate indistinguishable from negative controls. Chemical separation by the platelet GPIIb/IIIa receptor inhibitor eptifibatide decreased apoptosis by 66.6±10.6% (p = 0.008). Mice treated with eptifibatide in vivo survived longer following induction of sepsis than vehicle control mice.ConclusionsIn sepsis, platelet granzyme B-mediated apoptosis occurs in spleen and lung, and absence of granzyme B slows sepsis progression. This process proceeds in a contact-dependent manner that is inhibited ex vivo and in vivo by the platelet GPIIb/IIIa receptor inhibitor eptifibatide. The GPIIb/IIIa inhibitors and other classes of anti-platelet drugs may be protective in sepsis.

BackgroundAlthough rhinovirus infection is associated with increased risks of acute and chronic respiratory outcomes during childhood compared with respiratory syncytial virus (RSV), the underlying mechanisms remain unclear. We aimed to determine the differences in nasal airway microRNA profiles and their downstream effects between infants with rhinovirus and RSV bronchiolitis.MethodsAs part of a multicenter cohort study of infants hospitalized for bronchiolitis, we examined nasal samples obtained from 16 infants with rhinovirus and 16 infants with RSV. We tested nasal airway samples using microarrays to profile global microRNA expression and determine the predicted regulation of targeted transcripts. We also measured gene expression and cytokines for NFκB pathway components.ResultsBetween the virus groups, 386 microRNAs were differentially expressed (false discovery rate (FDR)<0.05). In infants with rhinovirus, the NFκB pathway was highly ranked as a predicted target for these differentially expressed microRNAs compared with RSV. Pathway analysis using measured mRNA expression data validated that rhinovirus infection had upregulation of NFκB family (RelA and NFκB2) and downregulation of inhibitor κB family. Infants with rhinovirus had higher levels of NFκB-induced type-2 cytokines (IL-10 and IL-13; FDR<0.01).ConclusionIn infants with bronchiolitis, rhinovirus and RSV infections had different nasal airway microRNA profiles associated with NFκB signaling.

BackgroundPediatric asthma is the most common chronic childhood disease in the USA, currently affecting ~ 7 million children. This heterogeneous syndrome is thought to encompass various disease phenotypes of clinically observable characteristics, which can be statistically identified by applying clustering approaches to patient clinical information. Extensive evidence has shown that the airway microbiome impacts both clinical heterogeneity and pathogenesis in pediatric asthma. Yet, so far, airway microbiotas have been consistently neglected in the study of asthma phenotypes. Here, we couple extensive clinical information with 16S rRNA high-throughput sequencing to characterize the microbiota of the nasal cavity in 163 children and adolescents clustered into different asthma phenotypes.ResultsOur clustering analyses identified three statistically distinct phenotypes of pediatric asthma. Four core OTUs of the pathogenic genera Moraxella, Staphylococcus, Streptococcus, and Haemophilus were present in at least 95% of the studied nasal microbiotas. Phyla (Proteobacteria, Actinobacteria, and Bacteroidetes) and genera (Moraxella, Corynebacterium, Dolosigranulum, and Prevotella) abundances, community composition, and structure varied significantly (0.05 < P ≤ 0.0001) across asthma phenotypes and one of the clinical variables (preterm birth). Similarly, microbial networks of co-occurrence of bacterial genera revealed different bacterial associations across asthma phenotypes.ConclusionsThis study shows that children and adolescents with different clinical characteristics of asthma also show different nasal bacterial profiles, which is indicative of different phenotypes of the disease. Our work also shows how clinical and microbial information could be integrated to validate and refine asthma classification systems and develop biomarkers of disease.Electronic supplementary materialThe online version of this article (10.1186/s40168-018-0564-7) contains supplementary material, which is available to authorized users.