ABSTRACT
High-energy, blunt force trauma to the abdomen results in an abdominal wall injury (AWI) in up to 9% of patients. In 1% of blunt abdominal trauma, they result in a traumatic abdominal wall hernia (TAWH). Optimal management of these injuries remains unclear. Because they are the result of a high-energy mechanism, concomitant serious abdominal organ injuries are common. This has prompted some to advocate that the presence of a TAWH on physical exam mandates exploratory laparotomy. However, delayed repairs have better outcomes and nontherapeutic celiotomy should be avoided. Similarly debated is the expanding use of minimally invasive techniques and the use of mesh for hernia repairs. Overall, the presence of a TAWH is likely not an absolute indication for emergency surgery. Rather, it is an indicator of high-energy impact and associated with a high rate of visceral injury. These patients require a close observation for clinical decline and development of typical indicators for laparotomy.
ABSTRACT
BACKGROUND: The critical blood shortage in January 2022 threatened the availability of blood. Utility of transfusion per unit was reported in a previous study, revealing patients receiving balanced transfusion are more likely to die after 16 units of packed red blood cells. We aimed to validate this study using a larger database. METHODS: Retrospective analysis utilizing the American College of Surgeons Trauma Quality Improvement Program was performed. Trauma patients aged ≥16 receiving transfusion within 4 hours of arrival were included and excluded if they died in the emergency department, received <2 units of packed red blood cells, did not receive fresh frozen plasma, or were missing data. Primary outcome was mortality. Subgroups were balanced transfusion if receiving ≤2:1 ratio of packed red blood cells:fresh frozen plasma, and unbalanced transfusion if >2:1 ratio. RESULTS: A total of 17,047 patients were evaluated with 28% mortality (4,822/17,408). Multivariable logistic regression identified advancing age (odds ratio 1.03 95% confidence interval 1.03-1.04), higher ISS (odds ratio 1.04, 95% confidence interval 1.03-1.04), and lower GCS (odds ratio 0.82, 95% confidence interval 0.82-0.83) as risk factors for mortality. Protective factors were balanced transfusion (odds ratio 0.81 95% confidence interval 0.71-0.93), male sex (odds ratio 0.90, 95% confidence interval 0.81-0.99), and blunt mechanism (odds ratio 0.74, 95% confidence interval 0.67-0.81). At 11 units of packed red blood cells, balanced transfusion patients were more likely to die (odds ratio 0.88, 95% confidence interval 0.80-0.98). Balanced transfusion patients survived at a higher rate for each unit of packed red blood cells, between 6 and 23 units of packed red blood cells. CONCLUSION: Mortality increases with each unit of packed red blood cell transfused. At 11 units of packed red blood cells, mortality is the more likely outcome. Balanced transfusion improves the chance of survival through 23 units of packed red blood cells.
Subject(s)
Blood Transfusion , Wounds and Injuries , Humans , Male , Retrospective Studies , Risk FactorsABSTRACT
Rationale: Asthma is a rhythmic inflammatory disease of the airway, regulated by the circadian clock. "Spill-over" of airway inflammation into the systemic circulation occurs in asthma and is reflected in circulating immune cell repertoire. The objective of the present study was to determine how asthma impacts peripheral blood diurnal rhythmicity. Methods: 10 healthy and 10 mild/moderate asthma participants were recruited to an overnight study. Blood was drawn every 6â h for 24â h. Main results: The molecular clock in blood cells in asthma is altered; PER3 is significantly more rhythmic in asthma compared to healthy controls. Blood immune cell numbers oscillate throughout the day, in health and asthma. Peripheral blood mononucleocytes from asthma patients show significantly enhanced responses to immune stimulation and steroid suppression at 16:00â h, compared to at 04:00â h. Serum ceramides show complex changes in asthma: some losing and others gaining rhythmicity. Conclusions: This is the first report showing that asthma is associated with a gain in peripheral blood molecular clock rhythmicity. Whether the blood clock is responding to rhythmic signals received from the lung or driving rhythmic pathology within the lung itself is not clear. Dynamic changes occur in serum ceramides in asthma, probably reflecting systemic inflammatory action. The enhanced responses of asthma blood immune cells to glucocorticoid at 16:00â h may explain why steroid administration is more effective at this time.
ABSTRACT
Seed pods represent an under-utilized and valuable dietary resource for zoos because they encourage naturalistic extractive foraging behavior and because seeds pods, like leafy browses, are more fiber-rich than most dietary items typically offered in zoos. The primary goal of this study was to examine the effects of honey locust (Gleditsia triacanthos) seed pods on the behavior and macronutrient intake of zoo-housed François' langurs (Trachypithecus francoisi; n = 3) and prehensile-tailed porcupines (Coendou prehensilis; n = 2) using a pre- versus postdiet implementation design. From December 2019 to April 2020, we recorded behavior using instantaneous interval sampling and daily macronutrient intake via dietary intake records. We found that time spent feeding increased (p < .001) and stereotypic behaviors decreased (p < .001) for the François' langur group during the seed pod phase. The prehensile-tailed porcupines also exhibited increased time spent feeding and decreased inactivity (p < .001 for all comparisons) during the experimental seed pod phase. We found no differences in macronutrient intake for the François' langur group. The female prehensile-tailed porcupine consumed more neutral detergent fiber (NDF) in the seed pod phase (p = .003) and the male consumed more crude protein, NDF, nonstructural carbohydrates, and crude fat (p < .001 for all comparisons). We stress that honey locust seed pods are a fiber-rich (i.e., ~40%-55% NDF by dry weight) dietary option for zoo-housed folivores and promote positive welfare by encouraging naturalistic foraging behavior and may help increase foraging time and decrease stereotypic behaviors.
Subject(s)
Grasshoppers , Honey , Presbytini , Female , Male , Animals , Animals, Zoo , Eating , Seeds , Feeding BehaviorABSTRACT
Eastern hellbenders Cryptobranchus alleganiensis alleganiensis, large aquatic salamanders, are declining over most of their range. The amphibian-killing fungus Batrachochytrium dendrobatidis (Bd) has contributed to global amphibian declines and has been detected on eastern hellbenders, but infection intensities were lower than those of species that are more susceptible to Bd. The factors limiting Bd on hellbenders may include antifungal metabolites produced by their skin microbiota. We used a metabolite fingerprinting technique to noninvasively identify the presence, but not identity, of metabolites associated with eastern hellbenders. We surveyed the skin of wild eastern hellbenders to test whether the composition and richness (i.e. number of metabolites) of their metabolites are explained by Bd status or location. Furthermore, we surveyed for metabolites on captive eastern hellbenders to test whether metabolite compositions were different between captive and wild eastern hellbenders. Bd detection was not associated with either metabolite richness or composition. Both metabolite composition and richness differed significantly on hellbenders from different locations (i.e. states). For metabolite composition, there was a statistical interaction between location and Bd status. Metabolite richness was greater on captive eastern hellbenders compared to wild hellbenders, and metabolite compositions differed between wild and captive eastern hellbenders. The methods we employed to detect metabolite profiles effectively grouped individuals by location even though metabolite composition and richness have high levels of intraspecific variation. Understanding the drivers and functional consequences of assemblages of skin metabolites on amphibian health will be an important step toward understanding the mechanisms that result in disease vulnerability.
Subject(s)
Chytridiomycota , Urodela , Animals , Urodela/microbiology , Amphibians , Batrachochytrium , Skin/microbiologyABSTRACT
Sea stars are keystone species and their mass die-offs due to sea star wasting disease (SSWD) impact marine communities and have fueled recent interest in the microbiome of sea stars. We assessed the host specificity of the microbiome associated with three body regions of the sea star Pisaster ochraceus using 16S rRNA gene amplicon surveys of the bacterial communities living on and in Pisaster, their environment, and sympatric marine hosts across three populations in British Columbia, Canada. Overall, the bacterial communities on Pisaster are distinct from their environment and differ by both body region and geography. We identified core bacteria specifically associated with Pisaster across populations and nearly absent in other hosts and the environment. We then investigated the distribution of these core bacteria on SSWD-affected Pisaster from one BC site and by reanalyzing a study of SSWD on Pisaster from California. We find no differences in the distribution of core bacteria in early disease at either site and two core taxa differ in relative abundance in advanced disease in California. Using phylogenetic analyses, we find that most core bacteria have close relatives on other sea stars and marine animals, suggesting these clades have evolutionary adaptions to an animal-associated lifestyle.
Subject(s)
Microbiota , Wasting Syndrome , Animals , Starfish/microbiology , Phylogeny , RNA, Ribosomal, 16S/geneticsABSTRACT
BACKGROUND: Balanced transfusion is lifesaving for hemorrhagic shock. The American Red Cross critical blood shortage in 2022 threatened the immediate availability of blood. To eliminate waste, we reviewed the utility of transfusions per unit to define expected mortality at various levels of balanced transfusion. METHODS: A retrospective study of 296 patients receiving massive transfusion on presentation at a level 1 trauma center was performed from January 2018 to December 2021. Units of packed red blood cells (PRBCs), fresh frozen plasma (FFP), and platelets received in the first 4 hours were recorded. Patients were excluded if they died in the emergency department, died on arrival, received <2 U PRBCs or FFP, or received PRBC/FFP >2:1. Primary outcomes were mortality and odds of survival to discharge. Subgroups were defined as transfused if receiving 2 to 9 U PRBCs, massive transfusion for 10 to 19 U PRBCs, and ultramassive transfusion for ≥20 U PRBCs. RESULTS: A total of 207 patients were included (median age, 32 years; median Injury Severity Score, 25; 67% with penetrating mechanism). Mortality was 29% (61 of 207 patients). Odds of survival is equal to odds of mortality at 11 U PRBCs (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.50-1.79). Beyond 16 U PRBCs, odds of mortality exceed survival (OR, 0.36; 95% CI, 0.16-0.82). Survival approaches zero >36 U PRBCs (OR, 0.09; 95% CI, 0.00-0.56). Subgroup mortality rates increased with unit transfused (16% transfused vs. 36% massive transfusion, p = 0.003; 36% massive transfusion vs. 67% ultramassive transfusion, p = 0.006). CONCLUSION: Mortality increases with each unit balanced transfusion. Surgeons should view efforts heroic beyond 16 U PRBCs/4 hours and near futile beyond 36 U PRBCs/4 hours. While extreme outliers can survive, consider cessation of resuscitation beyond 36 U PRBCs. This is especially true if hemostasis has not been achieved or blood supplies are limited. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level IV.
Subject(s)
Shock, Hemorrhagic , Wounds and Injuries , Humans , Adult , Blood Component Transfusion , Erythrocyte Transfusion , Retrospective Studies , Blood Transfusion , Shock, Hemorrhagic/therapy , Resuscitation , Wounds and Injuries/therapyABSTRACT
A 20-year-old woman with previous COVID-19 diagnosis presented with abdominal pain and colitis on CT scan. She was admitted in septic shock, with etiology of colitis unclear. After resuscitation, antibiotics, and steroids, she clinically deteriorated. Worsening Clostridioides difficile infection was most likely and she was taken to the operating room. Intraoperatively, only a segment of transverse colon appeared abnormal on gross and endoscopic evaluation. Total colectomy was deferred in favor of segmental resection. Given her unusual disease pattern and recent COVID-19 infection, diagnosis of MIS-C was considered. Steroids were continued and treatment broadened to include heparin and IVIG. The patient returned to the operating room for planned reexploration, endoscopy, and end colostomy. On hospital day three, the patient had an acute mental status change. Computed tomography demonstrated acute cerebral edema with brainstem herniation. The family chose comfort-care measures. Final pathology from the transverse colon demonstrated COVID-19-associated vasculitis.
Subject(s)
COVID-19 , Colitis , Colon, Transverse , Humans , Female , Young Adult , Adult , COVID-19 Testing , Colitis/diagnosis , Colitis/surgery , ColectomyABSTRACT
Chromatin immunoprecipitation (ChIP) maps, on a genome-wide scale, transcription factor binding sites, and the distribution of other chromatin-associated proteins and their modifications. As such, it provides valuable insights into mechanisms of gene regulation. However, successful ChIP experiments are dependent on the availability of a high-quality antibody against the target of interest. Using antibodies with poor sensitivity and specificity can yield misleading results. This can be partly circumvented by using epitope-tagged systems ( e.g. , HA, Myc, His), but these approaches are still antibody-dependent. HaloTag ® is a modified dehalogenase enzyme, which covalently binds synthetic ligands. This system can be used for imaging and purification of HaloTag ® fusion proteins, and has been used for ChIP in vitro . Here, we present a protocol for using the HaloTag ® system for ChIP in vivo , to map, with sensitivity and specificity, the cistrome of a dynamic mouse transcription factor expressed at its endogenous locus. Graphical abstract.
ABSTRACT
Many animals adjust the timing of seasonal events, such as reproduction, molt, migration, and hibernation, in response to interannual variation and directional climate-driven changes in temperature. However, the mechanisms by which temperature influences seasonal timing are relatively under-explored. Seasonal timing involves retrograde signaling in which thyrotropin (TSH) in the pars tuberalis (PT) alters expression of thyroid hormone (TH) deiodinases (Dio2/Dio3) in tanycyte cells lining the third ventricle of the hypothalamus. This, in turn, affects the availability of triiodothyronine (T3) within the mediobasal hypothalamus-increased hypothalamic T3 restores a summer phenotype and activates the reproductive axis in long-day breeders. Recently, we showed that retrograde TH signaling is activated during late hibernation in arctic ground squirrels (Urocitellus parryii) held in constant darkness and constant ambient temperature. Sensitivity of seasonal pathways to nonphotic cues, such as temperature, is likely particularly important to hibernating species that are sequestered in hibernacula during spring. To address this issue, we exposed captive arctic ground squirrels of both sexes to an ecologically relevant increase in ambient temperature (from -6 to -1°C) late in hibernation and examined the effects of warming on the seasonal retrograde TSH/Dio/T3 signaling pathway, as well as downstream elements of the reproductive axis. We found that warmed males tended to have higher PT TSHß expression and significantly heavier testis mass whereas the TSH/Dio/T3 signaling pathway was unaffected by warming in females, although warmed females exhibited a slight decrease in ovarian mass. Our findings suggest that temperature could have different effects on gonadal growth in male and female arctic ground squirrels, which could lead to mismatched timing in response to rapid climate change.
Subject(s)
Neuroendocrinology , Sciuridae , Male , Female , Animals , Seasons , Sciuridae/physiology , Reproduction/physiology , ThyrotropinABSTRACT
The circadian clock controls the physiological function of tissues through the regulation of thousands of genes in a cell-type-specific manner. The core cellular circadian clock is a transcription-translation negative feedback loop, which can recruit epigenetic regulators to facilitate temporal control of gene expression. Histone methyltransferase, mixed lineage leukemia gene 3 (MLL3) was reported to be required for the maintenance of circadian oscillations in cultured cells. Here, we test the role of MLL3 in circadian organization in whole animals. Using mice expressing catalytically inactive MLL3, we show that MLL3 methyltransferase activity is in fact not required for circadian oscillations in vitro in a range of tissues, nor for the maintenance of circadian behavioral rhythms in vivo. In contrast to a previous report, loss of MLL3-dependent methylation did not affect the global levels of H3K4 methylation in liver, indicating substantial compensation from other methyltransferases. Furthermore, we found little evidence of genomic repositioning of H3K4me3 marks. We did, however, observe repositioning of H3K4me1 from intronic regions to intergenic regions and gene promoters; however, there were no changes in H3K4me1 mark abundance around core circadian clock genes. Output functions of the circadian clock, such as control of inflammation, were largely intact in MLL3-methyltransferase-deficient mice, although some gene-specific changes were observed, with sexually dimorphic loss of circadian regulation of specific cytokines. Taken together, these observations indicate that MLL3-directed histone methylation is not essential for core circadian clock function; however, it may influence the inflammatory response.
Subject(s)
Circadian Clocks , Animals , Circadian Clocks/genetics , Circadian Rhythm , Histone Methyltransferases/genetics , Histone Methyltransferases/metabolism , Histone-Lysine N-Methyltransferase/metabolism , Methylation , Mice , Protein Processing, Post-TranslationalABSTRACT
Hibernation involves prolonged intervals of profound metabolic suppression periodically interrupted by brief arousals to euthermy, the function of which is unknown. Annual cycles in mammals are timed by a photoperiodically-regulated thyroid-hormone-dependent mechanism in hypothalamic tanycytes, driven by thyrotropin (TSH) in the pars tuberalis (PT), which regulates local TH-converting deiodinases and triggers remodeling of neuroendocrine pathways. We demonstrate that over the course of hibernation in continuous darkness, arctic ground squirrels (Urocitellus parryii) up-regulate the retrograde TSH/Deiodinase/TH pathway, remodel hypothalamic tanycytes, and activate the reproductive axis. Forcing the premature termination of hibernation by warming animals induced hypothalamic deiodinase expression and the accumulation of secretory granules in PT thyrotrophs and pituitary gonadotrophs, but did not further activate the reproductive axis. We suggest that periodic arousals may allow for the transient activation of hypothalamic thyroid hormone signaling, cellular remodeling, and re-programming of brain circuits in preparation for the short Arctic summer.
Subject(s)
Hibernation , Animals , Hibernation/physiology , Iodide Peroxidase , Sciuridae/physiology , Thyroid Hormones , ThyrotropinABSTRACT
The glucocorticoid receptor (GR) is a nuclear receptor critical to the regulation of energy metabolism and inflammation. The actions of GR are dependent on cell type and context. Here, we demonstrate the role of liver lineage-determining factor hepatocyte nuclear factor 4A (HNF4A) in defining liver specificity of GR action. In mouse liver, the HNF4A motif lies adjacent to the glucocorticoid response element (GRE) at GR binding sites within regions of open chromatin. In the absence of HNF4A, the liver GR cistrome is remodeled, with loss and gain of GR recruitment evident. Loss of chromatin accessibility at HNF4A-marked sites associates with loss of GR binding at weak GRE motifs. GR binding and chromatin accessibility are gained at sites characterized by strong GRE motifs, which show GR recruitment in non-liver tissues. The functional importance of these HNF4A-regulated GR sites is indicated by an altered transcriptional response to glucocorticoid treatment in the Hnf4a-null liver.
Subject(s)
Glucocorticoids , Receptors, Glucocorticoid , Animals , Chromatin/metabolism , Glucocorticoids/metabolism , Glucocorticoids/pharmacology , Hepatocyte Nuclear Factor 4/genetics , Hepatocyte Nuclear Factor 4/metabolism , Hepatocyte Nuclear Factors/metabolism , Liver/metabolism , Mice , Receptors, Glucocorticoid/metabolismABSTRACT
Chronic inflammation underpins many human diseases. Morbidity and mortality associated with chronic inflammation are often mediated through metabolic dysfunction. Inflammatory and metabolic processes vary through circadian time, suggesting an important temporal crosstalk between these systems. Using an established mouse model of rheumatoid arthritis, we show that chronic inflammatory arthritis results in rhythmic joint inflammation and drives major changes in muscle and liver energy metabolism and rhythmic gene expression. Transcriptional and phosphoproteomic analyses revealed alterations in lipid metabolism and mitochondrial function associated with increased EGFR-JAK-STAT3 signaling. Metabolomic analyses confirmed rhythmic metabolic rewiring with impaired ß-oxidation and lipid handling and revealed a pronounced shunt toward sphingolipid and ceramide accumulation. The arthritis-related production of ceramides was most pronounced during the day, which is the time of peak inflammation and increased reliance on fatty acid oxidation. Thus, our data demonstrate that localized joint inflammation drives a time-of-daydependent build-up of bioactive lipid species driven by rhythmic inflammation and altered EGFR-STAT signaling.
Subject(s)
Arthritis , Circadian Clocks , Circadian Rhythm/physiology , Energy Metabolism , Humans , Inflammation/metabolismABSTRACT
The mammalian circadian clock exerts control of daily gene expression through cycles of DNA binding. Here, we develop a quantitative model of how a finite pool of BMAL1 protein can regulate thousands of target sites over daily time scales. We used quantitative imaging to track dynamic changes in endogenous labelled proteins across peripheral tissues and the SCN. We determine the contribution of multiple rhythmic processes coordinating BMAL1 DNA binding, including cycling molecular abundance, binding affinities, and repression. We find nuclear BMAL1 concentration determines corresponding CLOCK through heterodimerisation and define a DNA residence time of this complex. Repression of CLOCK:BMAL1 is achieved through rhythmic changes to BMAL1:CRY1 association and high-affinity interactions between PER2:CRY1 which mediates CLOCK:BMAL1 displacement from DNA. Finally, stochastic modelling reveals a dual role for PER:CRY complexes in which increasing concentrations of PER2:CRY1 promotes removal of BMAL1:CLOCK from genes consequently enhancing ability to move to new target sites.
Subject(s)
Circadian Clocks , ARNTL Transcription Factors/genetics , ARNTL Transcription Factors/metabolism , Animals , CLOCK Proteins/genetics , CLOCK Proteins/metabolism , Circadian Clocks/genetics , Circadian Rhythm/genetics , Mammals/metabolismABSTRACT
The â¼20,000 cells of the suprachiasmatic nucleus (SCN), the master circadian clock of the mammalian brain, coordinate subordinate cellular clocks across the organism, driving adaptive daily rhythms of physiology and behavior. The canonical model for SCN timekeeping pivots around transcriptional/translational feedback loops (TTFL) whereby PERIOD (PER) and CRYPTOCHROME (CRY) clock proteins associate and translocate to the nucleus to inhibit their own expression. The fundamental individual and interactive behaviors of PER and CRY in the SCN cellular environment and the mechanisms that regulate them are poorly understood. We therefore used confocal imaging to explore the behavior of endogenous PER2 in the SCN of PER2::Venus reporter mice, transduced with viral vectors expressing various forms of CRY1 and CRY2. In contrast to nuclear localization in wild-type SCN, in the absence of CRY proteins, PER2 was predominantly cytoplasmic and more mobile, as measured by fluorescence recovery after photobleaching. Virally expressed CRY1 or CRY2 relocalized PER2 to the nucleus, initiated SCN circadian rhythms, and determined their period. We used translational switching to control CRY1 cellular abundance and found that low levels of CRY1 resulted in minimal relocalization of PER2, but yet, remarkably, were sufficient to initiate and maintain circadian rhythmicity. Importantly, the C-terminal tail was necessary for CRY1 to localize PER2 to the nucleus and to initiate SCN rhythms. In CRY1-null SCN, CRY1Δtail opposed PER2 nuclear localization and correspondingly shortened SCN period. Through manipulation of CRY proteins, we have obtained insights into the spatiotemporal behaviors of PER and CRY sitting at the heart of the TTFL molecular mechanism.
Subject(s)
Circadian Rhythm , Cryptochromes/metabolism , Period Circadian Proteins/metabolism , Suprachiasmatic Nucleus Neurons/metabolism , Animals , Circadian Rhythm/genetics , Fluorescent Antibody Technique , Gene Expression Regulation , Mice , Period Circadian Proteins/genetics , Protein Transport , Time-Lapse ImagingABSTRACT
The circadian clock component NR1D1 (REVERBα) is considered a dominant regulator of lipid metabolism, with global Nr1d1 deletion driving dysregulation of white adipose tissue (WAT) lipogenesis and obesity. However, a similar phenotype is not observed under adipocyte-selective deletion (Nr1d1Flox2-6:AdipoqCre), and transcriptional profiling demonstrates that, under basal conditions, direct targets of NR1D1 regulation are limited, and include the circadian clock and collagen dynamics. Under high-fat diet (HFD) feeding, Nr1d1Flox2-6:AdipoqCre mice do manifest profound obesity, yet without the accompanying WAT inflammation and fibrosis exhibited by controls. Integration of the WAT NR1D1 cistrome with differential gene expression reveals broad control of metabolic processes by NR1D1 which is unmasked in the obese state. Adipocyte NR1D1 does not drive an anticipatory daily rhythm in WAT lipogenesis, but rather modulates WAT activity in response to alterations in metabolic state. Importantly, NR1D1 action in adipocytes is critical to the development of obesity-related WAT pathology and insulin resistance.
Subject(s)
Adipocytes/metabolism , Adipose Tissue/metabolism , Nuclear Receptor Subfamily 1, Group D, Member 1/genetics , Obesity/genetics , Animals , Energy Metabolism , Gene Deletion , Lipid Metabolism , Male , Mice , Nuclear Receptor Subfamily 1, Group D, Member 1/metabolism , Obesity/metabolismABSTRACT
Robust inflammatory responses are critical to survival following respiratory infection, with current attention focused on the clinical consequences of the Coronavirus pandemic. Epigenetic factors are increasingly recognized as important determinants of immune responses, and EZH2 is a prominent target due to the availability of highly specific and efficacious antagonists. However, very little is known about the role of EZH2 in the myeloid lineage. Here, we show EZH2 acts in macrophages to limit inflammatory responses to activation, and in neutrophils for chemotaxis. Selective genetic deletion in macrophages results in a remarkable gain in protection from infection with the prevalent lung pathogen, pneumococcus. In contrast, neutrophils lacking EZH2 showed impaired mobility in response to chemotactic signals, and resulted in increased susceptibility to pneumococcus. In summary, EZH2 shows complex, and divergent roles in different myeloid lineages, likely contributing to the earlier conflicting reports. Compounds targeting EZH2 are likely to impair mucosal immunity; however, they may prove useful for conditions driven by pulmonary neutrophil influx, such as adult respiratory distress syndrome.