Motor Neurons Tune Premotor Activity in a Vertebrate Central Pattern Generator.

Central patterns generators (CPGs) are neural circuits that drive rhythmic motor output without sensory feedback. Vertebrate CPGs are generally believed to operate in a top-down manner in which premotor interneurons activate motor neurons that in turn drive muscles. In contrast, the frog (Xenopus laevis) vocal CPG contains a functionally unexplored neuronal projection from the motor nucleus to the premotor nucleus, indicating a recurrent pathway that may contribute to rhythm generation. In this study, we characterized the function of this bottom-up connection. The X. laevis vocal CPG produces a 50-60 Hz "fast trill" song used by males during courtship. We recorded "fictive vocalizations" in the in vitro CPG from the laryngeal nerve while simultaneously recording premotor activity at the population and single-cell level. We show that transecting the motor-to-premotor projection eliminated the characteristic firing rate of premotor neurons. Silencing motor neurons with the intracellular sodium channel blocker QX-314 also disrupted premotor rhythms, as did blockade of nicotinic synapses in the motor nucleus (the putative location of motor neuron-to-interneuron connections). Electrically stimulating the laryngeal nerve elicited primarily IPSPs in premotor neurons that could be blocked by a nicotinic receptor antagonist. Our results indicate that an inhibitory signal, activated by motor neurons, is required for proper CPG function. To our knowledge, these findings represent the first example of a CPG in which precise premotor rhythms are tuned by motor neuron activity.SIGNIFICANCE STATEMENT Central pattern generators (CPGs) are neural circuits that produce rhythmic behaviors. In vertebrates, motor neurons are not commonly known to contribute to CPG function, with the exception of a few spinal circuits where the functional significance of motor neuron feedback is still poorly understood. The frog hindbrain vocal circuit contains a previously unexplored connection from the motor to premotor region. Our results indicate that motor neurons activate this bottom-up connection, and blocking this signal eliminates normal premotor activity. These findings may promote increased awareness of potential involvement of motor neurons in a wider range of CPGs, perhaps clarifying our understanding of network principles underlying motor behaviors in numerous organisms, including humans.

The Gas2 family protein Pigs is a microtubule +TIP that affects cytoskeleton organisation.

Coordination between different cytoskeletal systems is crucial for many cell biological functions, including cell migration and mitosis, and also plays an important role during tissue morphogenesis. Proteins of the class of cytoskeletal crosslinkers, or cytolinkers, have the ability to interact with more than one cytoskeletal system at a time and are prime candidates to mediate any coordination. One such class comprises the Gas2-like proteins, combining a conserved calponin-homology-type actin-binding domain and a Gas2 domain predicted to bind microtubules (MTs). This domain combination is also found in spectraplakins, huge cytolinkers that play important roles in many tissues in both invertebrates and vertebrates. Here, we dissect the ability of the single Drosophila Gas2-like protein Pigs to interact with both actin and MT cytoskeletons, both in vitro and in vivo, and illustrate complex regulatory interactions that determine the localisation of Pigs to and its effects on the cytoskeleton.

Early intestinal development and mucin transcription in the young poult with probiotic and mannan oligosaccharide prebiotic supplementation.

Alternative and adjunctive approaches to decreasing the use of dietary antibiotics are becoming popular areas of study. Supplemental probiotics (commensal microbes) and prebiotics (indigestible complex carbohydrates) are 2 dietary approaches to facilitating the intestinal colonization of beneficial bacteria to compete with potential pathogens, thus creating a healthy mucosal environment. The intestinal mucosa is composed of mucin glycoproteins, which play a key role in preventing the attachment of pathogenic bacteria. At hatch, the neonatal turkey intestine is relatively aseptic and vulnderable to bacterial colonization by both commensal and pathogenic microbes. In the current study, we determined the transcription of MUC2, the primary mucin protein produced by goblet cells within the small intestine, and we also measured intestinal morphology immediately post-hatch through d 11. Poults were fed a conventional starter diet, the starter diet supplemented with one of 2 commercial probiotics (A, B), or a commercial mannan oligosaccharide. MUC2 transcription increased from d zero to d 4 post-hatch (P< 0.05), but there was no effect of probiotic or prebiotic supplementation. Villus height and villus area both increased with Probiotic B and mannan oligosaccharide supplementation (P<0.05) and there was a significant d X treatment interaction effect for crypt depth (P=0.007). These results suggest that probiotic and prebiotic supplementation can positively alter the intestinal microenvironment.

Temporal embryonic transcription of chicken fast skeletal myosin heavy chain isoforms in the single comb white leghorn.

There are numerous factors that can significantly influence embryonic development in poultry and thus make simple days of incubation (chronological age) a less than perfect metric for studying embryonic physiology. The developmental fast skeletal muscle myosin (MyHC), the predominant protein in the Pectoralis major (PM), is temporally expressed as a cadre of highly specific developmental isoforms. In the study described herein, a novel molecular technology (NanoString) was used to characterize the myosin isoform transcriptional patterns in the PM of Single Comb White Leghorn (SCWL) embryos. NanoString technology is based on quantitative analysis of the transcriptome through digital detection and quantification of target mRNA transcripts. Total RNA was isolated and gene transcription quantified using NanoString in embryonic muscle samples collected daily from 6 through 19 days of incubation. Data were analyzed using the LOESS smoothing function at a 95% confidence level. The temporal transcription of MyHC isoforms obtained in this study was consistent with the literature at higher specificity and resolution, thus validating NanoString for use in gene transcription analyses. The results support a hypothesis that the transcription patterns of the embryonic MyHC isoforms may be used as molecular clocks to further investigate the developmental relationships underlying embryonic fast skeletal muscle growth and development.

[Cytology of cerebrospinal fluid : Standards, importance and modern methods]. / Liquorzytologie : Standards, Stellenwert und moderne Methoden.

Cytology is an integral part of cerebrospinal fluid (CSF) analysis. It is relevant for the diagnostics and differential diagnosis of inflammatory, hemorrhagic and neoplastic central nervous system (CNS) processes. This article summarizes the recommended procedures and typical clinical patterns. In addition, modern immunocytochemical and flow cytometry methods for CSF cytology are presented. In particular, the diagnostic contribution and clinical relevance in several CNS conditions are discussed.

EULAR recommendations for the use of imaging in the diagnosis and management of spondyloarthritis in clinical practice.

A taskforce comprised of an expert group of 21 rheumatologists, radiologists and methodologists from 11 countries developed evidence-based recommendations on the use of imaging in the clinical management of both axial and peripheral spondyloarthritis (SpA). Twelve key questions on the role of imaging in SpA were generated using a process of discussion and consensus. Imaging modalities included conventional radiography, ultrasound, magnetic resonance imaging, computed tomography (CT), positron emission tomography, single photon emission CT, dual-emission x-ray absorptiometry and scintigraphy. Experts applied research evidence obtained from systematic literature reviews using MEDLINE and EMBASE to develop a set of 10 recommendations. The strength of recommendations (SOR) was assessed by taskforce members using a visual analogue scale. A total of 7550 references were identified in the search process, from which 158 studies were included in the systematic review. Ten recommendations were produced using research-based evidence and expert opinion encompassing the role of imaging in making a diagnosis of axial SpA or peripheral SpA, monitoring inflammation and damage, predicting outcome, response to treatment, and detecting spinal fractures and osteoporosis. The SOR for each recommendation was generally very high (range 8.9-9.5). These are the first recommendations which encompass the entire spectrum of SpA and evaluate the full role of all commonly used imaging modalities. We aimed to produce recommendations that are practical and valuable in daily practice for rheumatologists, radiologists and general practitioners.

Eukaryotic inhibitors or activators elicit responses to chemosensory compounds by ruminal isotrichid and entodiniomorphid protozoa.

Our objectives were to evaluate potential signaling pathways regulating rumen protozoal chemotaxis using eukaryotic inhibitors potentially coordinated with phagocytosis as assessed by fluorescent bead uptake kinetics. Wortmannin (inhibitor of phosphoinositide 3-kinase), insulin, genistein (purported inhibitor of a receptor tyrosine kinase), U73122 (inhibitor of phospholipase C), and sodium nitroprusside (Snp, nitric oxide generator, activating protein kinase G) were preincubated with mixed ruminal protozoa for 3h before assessing uptake of fluorescent beads and chemosensory behavior to glucose, peptides, and their combination; peptides were also combined with guanosine triphosphate (GTP; a chemorepellent). Entodiniomorphids were chemoattracted to both glucose and peptides, but chemoattraction to glucose was increased by Snp and wortmannin without effect on chemoattraction to peptides. Rate of fluorescent bead uptake by an Entodinium caudatum culture decreased when beads were added simultaneously with feeding and incubated with wortmannin (statistical interaction). Wortmannin also decreased the proportion of mixed entodiniomorphids consuming beads. Isotrichid protozoa exhibited greater chemotaxis to glucose but, compared with entodiniomorphids, were chemorepelled to peptides. Wortmannin increased chemotaxis by entodiniomorphids but decreased chemotaxis to glucose by isotrichids. Motility assays documented that Snp and wortmannin decreased net swimming speed (distance among 2 points per second) but not total swimming speed (including turns) by entodiniomorphids. Wortmannin decreased both net and total swimming behavior in isotrichids. Results mechanistically explain the isotrichid migratory ecology to rapidly take up newly ingested sugars and subsequent sedimentation back to the ventral reticulorumen. In contrast, entodiniomorphids apparently integrate cellular motility with feeding behavior to consume small particulates and thereby stay associated and pass with the degradable fraction of rumen particulates. These results extend findings from aerobic ciliate models to explain how rumen protozoa have adapted physiology for their specific ecological niches.

Comparative growth performance in different Japanese quail lines: the effect of muscle DNA content and fiber morphology.

The aim of this study was to investigate the DNA content and morphological characteristics of muscle fibers, and their relation to the growth performance in random bred control (RBC) and heavy weight (HW) Japanese quail lines. The 2 lines were of similar embryo size at 6 and 8 d of incubation; however, HW quail were significantly larger than their counterparts after 10 d of incubation (P < 0.05). The hatch weight of the HW quail line was approximately 1.3-fold higher than the RBC quail line (P < 0.001). After 15 d posthatch, the BW and pectoralis major muscle weight (PMW) exhibited remarkable differences between the 2 quail lines. The RBC line showed a faster rate of increase in PMW (2.7- vs. 2.1-fold) and total DNA mass (2.2- vs. 1.6-fold) between 0 and 4 d posthatch. The HW line exhibited a greater rate of the PMW (33.0- vs. 12.9-fold) and total DNA mass (10.3- vs. 4.0-fold) between 4 and 15 d posthatch than the RBC line. Moreover, the greatest increase in total DNA mass occurred between 0 and 8 d posthatch for the RBC line and 4 to 15 d posthatch for the HW line. These differences in the DNA content indicate a difference in the hypertrophic potential of muscle fibers between the 2 quail lines. The cross-sectional area of muscle fibers was 1.3-fold greater in the HW line compared with the RBC line at 8 d posthatch (158.5 vs. 97.11 µm(2), P < 0.001), and this difference increased with age (over 2.1-fold greater in the HW line). Thus, the most important time windows affecting ultimate body and muscle weights in the RBC and HW quail lines are between 0 to 8 d and 4 to 15 d posthatch, respectively. Rapid muscle growth rate and a greater muscle mass in the HW quail line may be partially due to the hypertrophic potential of muscle fibers, which is characterized by larger fiber size.

[Current cerebrospinal fluid diagnostics for pathogen-related diseases]. / Aktuelle Liquordiagnostik bei erregerbedingten Krankheiten.

Cerebrospinal fluid (CSF) analysis is of utmost importance to establish an early diagnosis of central nervous system (CNS) infections and to start appropriate therapy. The CSF white cell count, lactate concentration and total protein levels are usually available very quickly even from non-specialized laboratories and the combination of these parameters often provides sufficient information for decision-making in emergency cases. It is, however, not always possible to identify the underlying infective agent despite further CSF analyses, such as bacterial and fungal staining, evaluation of the blood-CSF barrier function, intrathecal immunoglobulin synthesis and oligoclonal IgG bands. Therefore, close communication between the laboratory and the clinician is an important prerequisite to specify additional pathogen-related diagnostic measures for successful confirmation of the diagnosis.

Factors contributing to variability of quantitative viral PCR results in proficiency testing samples: a multivariate analysis.

While viral load testing has gained widespread acceptance, a primary limitation remains the variability of results, particularly between different laboratories. While some work has demonstrated the importance of standardized quantitative control material in reducing this variability, little has been done to explore other important factors in the molecular amplification process. Results of 185 laboratories enrolled in the College of American Pathologists (CAP) 2009 viral load proficiency testing (PT) survey (VLS) were examined. This included 165 labs (89.2%) testing for cytomegalovirus (CMV), 99 (53.5%) for Epstein-Barr virus (EBV), and 64 (34.6%) for BK virus (BKV). At the time of PT, laboratories were asked a series of questions to characterize their testing methods. The responses to these questions were correlated to mean viral load (MVL) and result variability (RV). Contribution of individual factors to RV was estimated through analysis of variance (ANOVA) modeling and the use of backward selection of factors to fit those models. Selection of the quantitative calibrator, commercially prepared primers and probes, and amplification target gene were found most prominently associated with changes in MVL or RV for one or more of the viruses studied. Commercially prepared primers and probes and amplification target gene made the largest contribution to overall variability. Factors contributing to MVL and RV differed among viruses, as did relative contribution of each factor to overall variability. The marked variability seen in clinical quantitative viral load results is associated with multiple aspects of molecular testing design and performance. The reduction of such variability will require a multifaceted approach to improve the accuracy, reliability, and clinical utility of these important tests.

[Radiological differential diagnosis of rheumatoid arthritis]. / Radiologische Differenzialdiagnose der rheumatoiden Arthritis.

CLINICAL/METHODICAL ISSUE: Establishing an early and reliable diagnosis of rheumatoid arthritis (RA) is of major importance but can be a great clinical challenge leading to direct therapeutic consequences. No single epidemiological, genetic, clinical, serological or radiological test exists which can exclusively diagnose RA. STANDARD RADIOLOGICAL METHODS: In general diagnosis of RA includes a case history, clinical signs, laboratory abnormalities and radiological examinations, viz. conventional radiography of the joints of the hands and feet. PRACTICAL RECOMMENDATIONS: This review summarizes the most important radiological features of RA and the radiological findings of its closest differential diagnoses.

[Radiological imaging of osteoarthritis of the knee]. / Radiologische Bildgebung der Kniegelenkarthrose.

CLINICAL/METHODICAL ISSUE: Osteoarthritis is the most common degenerative age-related joint disease leading to typical degradation of articular cartilage with severe pain and limitation of joint motion. STANDARD RADIOLOGICAL METHODS: Although knee radiographs are widely considered as the gold standard for the assessment of knee osteoarthritis in clinical and scientific settings they increasingly have significant limitations in situations when resolution and assessment of cartilage is required. METHODICAL INNOVATIONS: Analysis of osteoarthritis of the knee with conventional x-ray is associated with many technical limitations and is increasingly being replaced by high-quality assessment using magnetic resonance imaging (MRI) or sonography both in the clinical routine and scientific studies. PERFORMANCE: Novel imaging modalities such as MRI or ultrasound enable in vivo visualization of the quality of the cartilaginous structure and bone as well as all articular and periarticular tissue. Therefore, the limitations of radiographs in assessment of knee osteoarthritis could be overcome by these techniques. This review article aims to provide insights into the most important radiological features of knee osteoarthritis and systematic visualization with different imaging approaches. PRACTICAL RECOMMENDATIONS: The demographic development in western industrialized countries predicts an increase of ageing-related osteoarthritis of the knee for the next decades. A systematic radiological evaluation of patients with knee osteoarthritis includes the assessment of the periarticular soft tissue, cartilaginous thickness, cartilage volume, possible cartilage defects, the macromodular network of hyaline cartilage, bone marrow edema, menisci and articular ligaments. Modern imaging modalities, such as MRI and sonography allow the limitations of conventional radiography to be overcome and to visualize the knee structures in great detail to quantitatively assess the severity of knee osteoarthritis.

Temporal myosin heavy chain isoform expression transitions faster in broiler chickens compared with Single Comb White Leghorns.

Myosin heavy chain (MyHC), one of the major components in the contractile machinery of skeletal muscle fibers, is found in several isoforms during myogenesis. During chicken development, embryonic, neonatal, and adult MyHC isoforms are expressed. Broiler chickens have been selected for fast and large muscle growth, whereas Single Comb White Leghorn (SCWL) chickens have been selected for egg laying capabilities. This has led to an obvious difference in muscle growth and development with broilers being much larger than SCWL. The objective of this study was to determine if differences in muscle growth and development of SCWL and broilers are associated with differences in temporal expression of MyHC isoforms in skeletal muscle between the 2 breeds. Pectoralis major muscle (PM) was collected from SCWL and broilers at embryonic d 15, 17, and 19 and 1, 5, 11, 20, 27, and 33 d posthatch with n = 3 samples per time point and breed. Western blotting using 3 monoclonal antibodies (EB165, 2E9, and AB8) was performed to compare the expression patterns of embryonic/adult, neonatal, and adult isoforms of MyHC, respectively, for all time points in both SCWL and broiler chickens. Both broiler and SCWL chickens began expressing the neonatal MyHC isoform on d 5; however, SCWL chickens expressed the neonatal isoform much longer than broilers. The SCWL chickens had sustained expression of the neonatal MyHC isoform through d 27, whereas in broiler chickens the neonatal isoform was not expressed at d 20. Pectoralis major tissue from broiler chickens expressed the adult MyHC isoform as early as d 20, whereas the SCWL chickens began expressing the adult isoform later. The rate of transition to neonatal and adult MyHC isoforms in broilers and Leghorns is consistent with the faster maturation and growth of broilers relative to Leghorns. This relationship between faster growth of the PM and the rate of transition of MyHC isoforms within the fast skeletal muscle of the PM may indicate a selection marker for improvement of broiler PM growth.

Comparative proteomic characterization of the sarcoplasmic proteins in the pectoralis major and supracoracoideus breast muscles in 2 chicken genotypes.

The selection processes that have resulted in broiler (meat) and leghorn (eggs) chickens have had very different effects on the pectoralis major and supracoracoideus muscles. The objective of this study, therefore, was to analyze the one-dimensional proteomic profiles of sarcoplasmic protein fractions isolated from the p. major and supracoracoideus muscles collected from 10 chicks from each genotype to compare developmental differences. The sarcoplasmic protein fraction was analyzed by SDS-PAGE. The mean band percentages were analyzed using a mixed model, with strain and muscle type as main effects. Six bands were found to be significantly different across the 2 strains. Strain differences in glycogen phosphorylase, enolase, elongation factor 1, creatine kinase, fructose-bisphosphate aldolase, and glyceraldehyde 3-phosphate-dehydrogenase suggest a genotype-specific shift in energy metabolism during breast muscle growth and development.

Feed restriction delays developmental fast skeletal muscle myosin heavy chain isoforms in turkey poults selected for differential growth.

Genetic selection has been very successful at significantly increasing BW and breast muscle proportion in commercial broiler and turkey strains. The mechanisms of breast muscle growth in poultry and the interactive effects of nutritional status and selection are not fully understood. The hypothesis underlying the current study is that feed restriction, simply as a vehicle for controlling early growth, would delay the temporal expression pattern of neonatal (nMyHC) and adult (aMyHC) fast skeletal muscle myosin heavy chain (MyHC) isoforms in the pectoralis major muscle of turkey poults. The poultry growth model used to evaluate this hypothesis consisted of a randombred control turkey line (RBC2) that represents commercial turkeys of the 1960s and a line developed from the RBC2 by selection for BW at 16 wk of age (F line). The F line has significantly heavier breast muscles than the RBC2 concomitant with increased BW, but the proportion of breast muscle relative to BW is similar. A quantitative indirect ELISA using fast skeletal MyHC isoform specific monoclonal antibodies revealed no significant line differences in the temporal expression of posthatch fast skeletal muscle MyHC in ad libitum fed poults. Feed restriction, however, altered the temporal expression patterns of nMyHC and aMyHC in both F line and RBC2 poults compared with the poults fed ad libitum.

The Drosophila spectraplakin Short stop regulates focal adhesion dynamics by cross-linking microtubules and actin.

The spectraplakin family of proteins includes ACF7/MACF1 and BPAG1/dystonin in mammals, VAB-10 in Caenorhabditis elegans, Magellan in zebrafish, and Short stop (Shot), the sole Drosophila member. Spectraplakins are giant cytoskeletal proteins that cross-link actin, microtubules, and intermediate filaments, coordinating the activity of the entire cytoskeleton. We examined the role of Shot during cell migration using two systems: the in vitro migration of Drosophila tissue culture cells and in vivo through border cell migration. RNA interference (RNAi) depletion of Shot increases the rate of random cell migration in Drosophila tissue culture cells as well as the rate of wound closure during scratch-wound assays. This increase in cell migration prompted us to analyze focal adhesion dynamics. We found that the rates of focal adhesion assembly and disassembly were faster in Shot-depleted cells, leading to faster adhesion turnover that could underlie the increased migration speeds. This regulation of focal adhesion dynamics may be dependent on Shot being in an open confirmation. Using Drosophila border cells as an in vivo model for cell migration, we found that RNAi depletion led to precocious border cell migration. Collectively, these results suggest that spectraplakins not only function to cross-link the cytoskeleton but may regulate cell-matrix adhesion.

Contrast-enhanced ultrasonography for the detection of joint vascularity in arthritis--subjective grading versus computer-aided objective quantification.

PURPOSE: To compare joint inflammation assessment using subjective grading of power Doppler ultrasonography (PDUS) and contrast-enhanced ultrasonography (CEUS) versus computer-aided objective CEUS quantification. MATERIALS AND METHODS: 37 joints of 28 patients with arthritis of different etiologies underwent B-mode ultrasonography, PDUS, and CEUS using a second-generation contrast agent. Synovial thickness, extent of vascularized pannus and intensity of vascularization were included in a 4-point PDUS and CEUS grading system. Subjective CEUS and PDUS scores were compared to computer-aided objective CEUS quantification using Qontrast® software for the calculation of the signal intensity (SI) and the ratio of SI for contrast enhancement. RESULTS: The interobserver agreement for subjective scoring was good to excellent (κ = 0.8 - 1.0; P < 0.0001). Computer-aided objective CEUS quantification correlated statistically significantly with subjective CEUS (P < 0.001) and PDUS grading (P < 0.05). The Qontrast® SI ratio correlated with subjective CEUS (P < 0.02) and PDUS grading (P < 0.03). Clinical activity did not correlate with vascularity or synovial thickening (P = N. S.) and no correlation between synovial thickening and vascularity extent could be found, neither using PDUS nor CEUS (P = N. S.). CONCLUSION: Both subjective CEUS grading and objective CEUS quantification are valuable for assessing joint vascularity in arthritis and computer-aided CEUS quantification may be a suitable objective tool for therapy follow-up in arthritis.

Multivariate evaluation of 1-dimensional sarcoplasmic protein profile patterns of turkey breast muscle during early post-hatch development.

Proteins are the main participants in metabolic pathways. However, the analysis of protein abundance patterns associated with those pathways is complicated by the large number of proteins involved. In this study, the objective was to present the application of principal component analysis (PCA) to permit the visualization of developmental proteomic patterns of sarcoplasmic proteins found in breast muscle. Different turkey genotypes and nutritional regimens were used to potentially increase the variability within the sarcoplasmic protein profile. Sarcoplasmic protein fractions from turkey breast muscle samples were collected at 6 ages between 7 to 24 d. Breast muscle samples were collected from 2 distinctly different turkey lines. The poults within each line were either ad libitum or restrict fed. Proteomic PCA plots showed a visual developmental pattern from 7 until 17 d. Multivariate ANOVA highlighted the effect of time point and feeding regimen among profile patterns. The use of different genotypes and feeding regimens influenced variability, which was measured by mean Euclidean distances and ellipses of the PCA plots. These treatment effects, however, did not mask the developmental patterns. After 17 d, the proteomic patterns converged, suggesting that a level of biological stability was achieved regardless of the genotype or treatment. The developmental pattern obtained by the PCA methodology can aid in the planning of more efficient experimental designs so the developmental stage of individuals can be more accurately assessed.

Salmonella-induced apoptosis of infected macrophages results in presentation of a bacteria-encoded antigen after uptake by bystander dendritic cells.

Salmonella typhimurium is a gram-negative bacterium that survives and replicates inside vacuolar compartments of macrophages. Infection of macrophages with S. typhimurium grown under conditions allowing expression of the type III secretion system results in apoptotic death of the infected cells. Here, we show that infection of bone marrow-derived macrophages (MPhi) with wild-type S. typhimurium 14028 results in presentation of epitopes derived from a bacteria-encoded antigen on major histocompatibility complex (MHC) class I and MHC class II molecules after internalization of apoptotic MPhi by bystander dendritic cells (DCs). In contrast, infection of MPhi with the phoP constitutive mutant strain CS022, which does not induce apoptosis in infected MPhi, does not result in presentation of a bacteria-derived antigen by bystander DCs unless the infected MPhi are induced to undergo apoptosis by treatment with lipopolysaccharide and ATP. DCs appear to be unique in their ability to present antigens derived from MPhi induced to undergo apoptosis by Salmonella, as bystander MPhi are not capable of presenting the bacteria-derived antigen despite the fact that they efficiently internalize the apoptotic cells. These data suggest that apoptosis induction by bacterial infection of MPhi may not be a quiescent death that allows the bacteria to escape recognition by the immune system, but rather may contribute to an antimicrobial immune response upon engulfment by bystander DCs.