Toll-like receptors matter: plasmacytoid dendritic cells in COVID-19.

Plasmacytoid dendritic cells (pDC) have the unique ability to rapidly mount high-level antiviral type I interferon (IFN-I) responses during diverse virus infections. In COVID-19 patients, reduced pDC numbers correlate with diminished IFN-I serum levels and enhanced disease severity. However, the molecular mechanisms underlying SARS-CoV-2-mediated pDC stimulation to induce cytokine responses are still largely unclear. In this issue of the EMBO Journal, van der Sluis and colleagues tackled this question by using an innovative hematopoietic stem and progenitor cells (HSPC)-pDC system that allows gene editing and the detailed analysis of pDC sensing mechanisms.

Dynamic interactome of the MHC I peptide loading complex in human dendritic cells.

Dendritic cells (DCs) orchestrate immune responses by presenting antigenic peptides on major histocompatibility complex (MHC) molecules to T cells. Antigen processing and presentation via MHC I rely on the peptide-loading complex (PLC), a supramolecular machinery assembled around the transporter associated with antigen processing (TAP), which is the peptide transporter in the endoplasmic reticulum (ER) membrane. We studied antigen presentation in human DCs by isolating monocytes from blood and differentiating them into immature and mature DCs. We uncovered that during DC differentiation and maturation, additional proteins are recruited to the PLC, including B-cell receptor-associated protein 31 (BAP31), vesicle-associated membrane protein-associated protein A (VAPA), and extended synaptotagmin-1 (ESYT1). We demonstrated that these ER cargo export and contact site-tethering proteins colocalize with TAP and are within 40 nm proximity of the PLC, suggesting that the antigen processing machinery is located near ER exit- and membrane contact sites. While CRISPR/Cas9-mediated deletion of TAP and tapasin significantly reduced MHC I surface expression, single-gene deletions of the identified PLC interaction partners revealed a redundant role of BAP31, VAPA, and ESYT1 in MHC I antigen processing in DCs. These data highlight the dynamics and plasticity of PLC composition in DCs that previously was not recognized by the analysis of cell lines.

Indigenous Populations of a Biological Control Agent in Agricultural Field Soils Predicted Suppression of a Plant Pathogen.

The nematophagous fungus Hyalorbilia oviparasitica and relatives (Hyalorbilia spp.) are known to parasitize several endoparasitic nematodes. In this project, we hypothesized that indigenous populations of this fungus could be used to predict nematode suppression in agricultural field soils. We quantified Hyalorbilia spp. in soil samples from 44 different sugar beet fields in the Imperial Valley of California. Seven soils harboring Hyalorbilia spp. and two that tested negative for the fungi were examined for nematode suppressive activity. Untreated and autoclaved portions of each soil were planted with cabbage and infested with sugar beet cyst nematode (Heterodera schachtii) juveniles. Females and cysts of H. schachtii were enumerated after 12 weeks. In the seven soils harboring Hyalorbilia spp., females and cysts in the untreated soils were reduced by 61 to 82% compared with the autoclaved controls. Soils with no detectable Hyalorbilia spp. exhibited no nematode suppression. Two novel Hyalorbilia strains, HsImV25 and HsImV27, were isolated from H. schachtii females reared in field soil using an enrichment and double-baiting cultivation technique. Both strains suppressed H. schachtii populations by more than 80% in soil-based assays, confirming that Hyalorbilia spp. are the likely causal agents of the nematode suppression in these soils. This study demonstrated that indigenous populations of a hyperparasite (Hyalorbilia spp.) in agricultural field soils predicted suppressive activity against a soilborne plant pathogen (H. schachtii). To our knowledge, this is the first report to demonstrate this capability. We anticipate that this research will provide a blueprint for other similar studies, thereby advancing the field of soilborne biological control.

Nanoscale organization of the MHC I peptide-loading complex in human dendritic cells.

Dendritic cells (DCs) translate local innate immune responses into long-lasting adaptive immunity by priming antigen-specific T cells. Accordingly, there is an ample interest in exploiting DCs for therapeutic purposes, e.g., in personalized immunotherapies. Despite recent advances in elucidating molecular pathways of antigen processing, in DCs the exact spatial organization of the underlying processes is largely unknown. Here, we unraveled the nanoscale organization of the transporter associated with antigen processing (TAP)-dependent peptide-loading machinery in human monocyte-derived DCs (moDC). We detected an unexpected accumulation of MHC I peptide-loading complexes (PLCs) and TAP-dependent peptide compartmentalization in protrusions of activated DCs. Using single-molecule localization microscopy we revealed that PLCs display homogeneously sized assemblies, independent of the DC activation status or cellular localization. Our data indicate that moDCs show augmentation of subcellular PLC density during DC maturation. We observed a twofold density increase in the cell body, while an even fourfold accumulation was detected in the tips of the protrusions at the mature DC stage in comparison to immature DCs. In these tip regions, PLC assemblies are found along highly compressed tubular ER networks. These findings provide novel insights into nanoscale organization of the antigen presentation machinery, and open new perspectives on the T cell stimulatory capacity of DCs.

Iodenium or Phosphonium: The Ambi-Valent Character of Iodophosphonium Complexes.

The ambi-valent character of the P-I bond in iodophosphonium complexes ensures that it can be electrophilic at either P or I. Herein, we use an ensemble of computational tools and methodologies to probe the nature of this ambi-valent bond. Geometric and atomic electron population analyses yielded strong trends between the electron donating ability of the phosphine and the strength and polarity of the P-I bond. Quasi-atomic orbital analysis demonstrated the near homo-polarity of the P-I bond, and energy decomposition analysis calculations demonstrated the ability to tune the polarization of the bond with only mild changes in secondary structural features. Finally, the ambi-valent nature of the P-I bond was demonstrated to follow hard-soft considerations in reactions with nucleophiles, with harder nucleophiles preferentially forming products of addition to P and softer nucleophiles to I.

Posttreatment Imaging of the Wrist and Hand: Update 2022.

Common indications for surgical procedures of the wrist and hand include acute fractures or fracture-dislocations; nonunited fractures; posttraumatic, degenerative, and inflammatory arthritides and tendinopathies; injuries to tendons, ligaments, and the triangular fibrocartilage complex; and entrapment neuropathies. Soft tissue or osseous infections or masses may also need surgical treatment. Several of these procedures require surgical hardware placement, and most entail clinical follow-up with periodic imaging. Radiography should be the first imaging modality in the evaluation of the postoperative wrist and hand. Computed tomography, magnetic resonance imaging, diagnostic ultrasonography, and occasionally nuclear medicine studies may be performed to diagnose or better characterize suspected postoperative complications. To provide adequate evaluation of postoperative imaging of the wrist and hand, the interpreting radiologist must be familiar with the basic principles of these surgical procedures and both the imaging appearance of normal postoperative findings as well as the potential complications.

Deletion of the proton receptor OGR1 in mouse osteoclasts impairs metabolic acidosis-induced bone resorption.

Metabolic acidosis induces osteoclastic bone resorption and inhibits osteoblastic bone formation. Previously we found that mice with a global deletion of the proton receptor OGR1 had increased bone density although both osteoblast and osteoclast activity were increased. To test whether direct effects on osteoclast OGR1 are critical for metabolic acidosis stimulated bone resorption, we generated knockout mice with an osteoclast-specific deletion of OGR1 (knockout mice). We studied bones from three-month old female mice and the differentiated osteoclasts derived from bone marrow of femurs from these knockout and wild type mice. MicroCT demonstrated increased density in tibiae and femurs but not in vertebrae of the knockout mice. Tartrate resistant acid phosphatase staining of tibia indicated a decrease in osteoclast number and surface area/bone surface from knockout compared to wild type mice. Osteoclasts derived from the marrow of knockout mice demonstrated decreased pit formation, osteoclast staining and osteoclast-specific gene expression compared to those from wild type mice. In response to metabolic acidosis, osteoclasts from knockout mice had decreased nuclear translocation of NFATc1, a transcriptional regulator of differentiation, and no increase in size or number compared to osteoclasts from wild type mice. Thus, loss of osteoclast OGR1 decreased both basal and metabolic acidosis-induced osteoclast activity indicating osteoclast OGR1 is important in mediating metabolic acidosis-induced bone resorption. Understanding the role of OGR1 in metabolic acidosis-induced bone resorption will provide insight into bone loss in acidotic patients with chronic kidney disease.

Interferon-beta expression and type I interferon receptor signaling of hepatocytes prevent hepatic necrosis and virus dissemination in Coxsackievirus B3-infected mice.

During Coxsackievirus B3 (CVB3) infection hepatitis is a potentially life threatening complication, particularly in newborns. Studies with type I interferon (IFN-I) receptor (IFNAR)-deficient mice revealed a key role of the IFN-I axis in the protection against CVB3 infection, whereas the source of IFN-I and cell types that have to be IFNAR triggered in order to promote survival are still unknown. We found that CVB3 infected IFN-ß reporter mice showed effective reporter induction, especially in hepatocytes and only to a minor extent in liver-resident macrophages. Accordingly, upon in vitro CVB3 infection of primary hepatocytes from murine or human origin abundant IFN-ß responses were induced. To identify sites of IFNAR-triggering we performed experiments with Mx reporter mice, which upon CVB3 infection showed massive luciferase induction in the liver. Immunohistological studies revealed that during CVB3 infection MX1 expression of hepatocytes was induced primarily by IFNAR-, and not by IFN-III receptor (IFNLR)-triggering. CVB3 infection studies with primary human hepatocytes, in which either the IFN-I or the IFN-III axis was inhibited, also indicated that primarily IFNAR-, and to a lesser extent IFNLR-triggering was needed for ISG induction. Interestingly, CVB3 infected mice with a hepatocyte-specific IFNAR ablation showed severe liver cell necrosis and ubiquitous viral dissemination that resulted in lethal disease, as similarly detected in classical IFNAR-/- mice. In conclusion, we found that during CVB3 infection hepatocytes are major IFN-I producers and that the liver is also the organ that shows strong IFNAR-triggering. Importantly, hepatocytes need to be IFNAR-triggered in order to prevent virus dissemination and to assure survival. These data are compatible with the hypothesis that during CVB3 infection hepatocytes serve as important IFN-I producers and sensors not only in the murine, but also in the human system.

Attentional Bias Towards Visual Itch and Pain Stimuli in Itch- and Pain-free Individuals?

Itch and pain are important attention-demanding sensations that allow adaptive responses to potential bodily harm. An attentional bias towards itch and pain stimuli, i.e. preferential attention allocation towards itch- and pain-related information, has been found in healthy, as well as patient groups. However, it remains unclear whether attentional bias for itch and pain differs from a general bias towards negative information. Therefore, this study investigated attentional bias towards itch and pain in 70 itch- and pain-free individuals. In an attention task, itch- and pain-related stimuli, as well as negative stimuli, were presented alongside neutral stimuli. The results did not indicate an attentional bias towards itch-, pain-, and negative visual information. This finding suggests that people without itch and pain symptoms do not prioritize itch- and pain-related information above neutral information. Future research should investigate whether attention towards itch- and pain-related information might be biased in patients with chronic itch and pain.

Preferential uptake of chitosan-coated PLGA nanoparticles by primary human antigen presenting cells.

Biodegradable polymeric nanoparticles (NP) made from poly (lactid-co-glycolide) acid (PLGA) and chitosan (CS) hold promise as innovative formulations for targeted delivery. Since interactions of such NP with primary human immune cells have not been characterized, yet, here we assessed the effect of PLGA or CS-PLGA NP treatment on human peripheral blood mononuclear cells (PBMC), as well as on monocyte-derived DC (moDC). Amongst PBMC, antigen presenting cells (APC) showed higher uptake of both NP preparations than lymphocytes. Furthermore, moDC internalized CS-PLGA NP more efficiently than PLGA NP, presumably because of receptor-mediated endocytosis. Consequently, CS-PLGA NP were delivered mostly to endosomal compartments, whereas PLGA NP primarily ended up in lysosomes. Thus, CS-PLGA NP confer enhanced delivery to endosomal compartments of APC, offering new therapeutic options to either induce or modulate APC function and to inhibit pathogens that preferentially infect APC.

The role of diffusion tensor imaging in the diagnosis, prognosis, and assessment of recovery and treatment of spinal cord injury: a systematic review.

OBJECTIVEDiffusion tensor imaging (DTI) is an MRI tool that provides an objective, noninvasive, in vivo assessment of spinal cord injury (SCI). DTI is significantly better at visualizing microstructures than standard MRI sequences. In this imaging modality, the direction and amplitude of the diffusion of water molecules inside tissues is measured, and this diffusion can be measured using a variety of parameters. As a result, the potential clinical application of DTI has been studied in several spinal cord pathologies, including SCI. The aim of this study was to describe the current state of the potential clinical utility of DTI in patients with SCI and the challenges to its use as a tool in clinical practice.METHODSA search in the PubMed database was conducted for articles relating to the use of DTI in SCI. The citations of relevant articles were also searched for additional articles.RESULTSAmong the most common DTI metrics are fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. Changes in these metrics reflect changes in tissue integrity. Several DTI metrics and combinations thereof have demonstrated significant correlations with clinical function both in model species and in humans. Its applications encompass the full spectrum of the clinical assessment of SCI including diagnosis, prognosis, recovery, and efficacy of treatments in both the spinal cord and potentially the brain.CONCLUSIONSDTI and its metrics have great potential to become a powerful clinical tool in SCI. However, the current limitations of DTI preclude its use beyond research and into clinical practice. Further studies are needed to significantly improve and resolve these limitations as well as to determine reliable time-specific changes in multiple DTI metrics for this tool to be used accurately and reliably in the clinical setting.

[Workload and health of workers with a migrant background]. / Arbeitsbelastung und Gesundheit von Erwerbstätigen mit Migrationshintergrund.

BACKGROUND AND OBJECTIVES: Diversity is increasing, including among workers. Traditional approaches in occupational safety and health are no longer sufficient to meet the emerging challenges in the workplace. Currently, knowledge about specific needs of workers with a migrant background is insufficient to develop suitable interventions under participatory methods. The aim of this work is to gain knowledge about diversity in the workplace and discuss considerations for suitable prevention and health promotion. MATERIALS AND METHODS: Research in reports, analyses of the German Socio-Economic Panel, as well as a review of the literature in relevant databases served to collate current findings about health indicators, stress and strain, structural conditions, and occupational prevention and health promotion. RESULTS: Differentiated results about health in the workplace and stress and strain could be identified. In particular, workers with a migrant background are more often exposed to physical stress and harsh environmental conditions. Furthermore, structural conditions are worse for these workers, e.g. due to lower employment rates, as well as enhanced atypical employment among the target group. CONCLUSION: Plausible explanations for the reported differences are discussed and useful implications are given. However, the overall lack of data and challenges in data collection must be considered.

Physics for clinicians: Fluid-attenuated inversion recovery (FLAIR) and double inversion recovery (DIR) Imaging.

A pedagogical review of fluid-attenuated inversion recovery (FLAIR) and double inversion recovery (DIR) imaging is conducted in this article. The basics of the two pulse sequences are first described, including the details of the inversion preparation and imaging sequences with accompanying mathematical formulae for choosing the inversion time in a variety of scenarios for use on clinical MRI scanners. Magnetization preparation (or T2prep), a strategy for improving image signal-to-noise ratio and contrast and reducing T1 weighting at high field strengths, is also described. Lastly, image artifacts commonly associated with FLAIR and DIR are described with clinical examples, to help avoid misdiagnosis. LEVEL OF EVIDENCE: 5 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1590-1600.

Glyceryl Trinitrate for Acute Intracerebral Hemorrhage: Results From the Efficacy of Nitric Oxide in Stroke (ENOS) Trial, a Subgroup Analysis.

BACKGROUND AND PURPOSE: The Efficacy of Nitric Oxide in Stroke (ENOS) trial found that transdermal glyceryl trinitrate (GTN, a nitric oxide donor) lowered blood pressure but did not improve functional outcome in patients with acute stroke. However, GTN was associated with improved outcome if patients were randomized within 6 hours of stroke onset. METHODS: In this prespecified subgroup analysis, the effect of GTN (5 mg/d for 7 days) versus no GTN was studied in 629 patients with intracerebral hemorrhage presenting within 48 hours and with systolic blood pressure ≥140 mm Hg. The primary outcome was the modified Rankin Scale at 90 days. RESULTS: Mean blood pressure at baseline was 172/93 mm Hg and significantly lower (difference -7.5/-4.2 mm Hg; both P≤0.05) on day 1 in 310 patients allocated to GTN when compared with 319 randomized to no GTN. No difference in the modified Rankin Scale was observed between those receiving GTN versus no GTN (adjusted odds ratio for worse outcome with GTN, 1.04; 95% confidence interval, 0.78-1.37; P=0.84). In the subgroup of 61 patients randomized within 6 hours, GTN improved functional outcome with a shift in the modified Rankin Scale (odds ratio, 0.22; 95% confidence interval, 0.07-0.69; P=0.001). There was no significant difference in the rates of serious adverse events between GTN and no GTN. CONCLUSIONS: In patients with intracerebral hemorrhage within 48 hours of onset, GTN lowered blood pressure was safe but did not improve functional outcome. Very early treatment might be beneficial but needs assessment in further studies. CLINICAL TRIAL REGISTRATION: URL: http://www.isrctn.com/ISRCTN99414122. Unique identifier: 99414122.

Convergent Validity of Three Methods for Measuring Postoperative Complications.

BACKGROUND: Anesthesiologists need tools to accurately track postoperative outcomes. The accuracy of patient report in identifying a wide variety of postoperative complications after diverse surgical procedures has not previously been investigated. METHODS: In this cohort study, 1,578 adult surgical patients completed a survey at least 30 days after their procedure asking if they had experienced any of 18 complications while in the hospital after surgery. Patient responses were compared to the results of an automated electronic chart review and (for a random subset of 750 patients) to a manual chart review. Results from automated chart review were also compared to those from manual chart review. Forty-two randomly selected patients were contacted by telephone to explore reasons for discrepancies between patient report and manual chart review. RESULTS: Comparisons between patient report, automated chart review, and manual chart review demonstrated poor-to-moderate positive agreement (range, 0 to 58%) and excellent negative agreement (range, 82 to 100%). Discordance between patient report and manual chart review was frequently explicable by patients reporting events that happened outside the time period of interest. CONCLUSIONS: Patient report can provide information about subjective experiences or events that happen after hospital discharge, but often yields different results from chart review for specific in-hospital complications. Effective in-hospital communication with patients and thoughtful survey design may increase the quality of patient-reported complication data.

Tissue-Negative Transient Ischemic Attack: Is There a Role for Perfusion MRI?

OBJECTIVE: Approximately 60% of patients with a clinical transient ischemic attack (TIA) do not have DWI evidence of cerebral ischemia. The purpose of this study was to assess the added diagnostic value of perfusion MRI in the evaluation of patients with TIA who have normal DWI findings. MATERIALS AND METHODS: The inclusion criteria for this retrospective study were clinical presentation of TIA at admission with a discharge diagnosis of TIA confirmed by a stroke neurologist, MRI including both DWI and perfusion-weighted imaging within 48 hours of symptom onset, and no DWI lesion. Cerebral blood flow (CBF) and time to maximum of the residue function (Tmax) maps were evaluated independently by two observers. Multivariate analysis was used to assess perfusion findings; clinical variables; age, blood pressure, clinical symptoms, diabetes (ABCD2) score; duration of TIA; and time between MRI and onset and resolution of symptoms. RESULTS: Fifty-two patients (33 women, 19 men; age range, 20-95 years) met the inclusion criteria. A regional perfusion abnormality was identified on either Tmax or CBF maps of 12 of 52 (23%) patients. Seven (58%) of the patients with perfusion abnormalities had hypoperfused lesions best detected on Tmax maps; the other five had hyperperfusion best detected on CBF maps. In 11 of 12 (92%) patients with abnormal perfusion MRI findings, the regional perfusion deficit correlated with the initial neurologic deficits. Multivariable analysis revealed no significant difference in demographics, ABCD2 scores, or presentation characteristics between patients with and those without perfusion abnormalities. CONCLUSION: Perfusion MRI that includes Tmax and CBF parametric maps adds diagnostic value by depicting regions with delayed perfusion or postischemic hyperperfusion in approximately one-fourth of TIA patients who have normal DWI findings.

Fractures of the posterolateral maxillary sinus: a masticator space blowout injury?

BACKGROUND AND PURPOSE: Segmental, depressed fractures of the posterolateral maxillary sinus may occur as a result of trauma to the masticator space, previously described in association with mandibular fractures. The authors hypothesize that the fracture is due to a transient increase in pressure in the masticator space (blow out) and therefore should be seen in association with other regional fractures. MATERIALS AND METHODS: Injuries of the masticator space were retrospectively identified by searching the imaging database from January 2014 to November 2014 for keywords that would identify regional trauma. The images were reviewed for segmental depressed fractures in the posterolateral aspect of the maxillary sinus accompanied by herniation of a variable amount of masticator space fat and/or muscle into the adjacent sinus. Three neuroradiologists reviewed the images and agreed by consensus on the presence or absence of a masticator space blowout fracture. RESULTS: Forty-three zygomaticomaxillary complex (ZMC) fractures, 89 mandibular fractures, and 49 isolated zygomatic arch fractures were identified. While all of the ZMC fractures had a maxillary component, 3 of 43 (7.0 %) additional fractures met our fracture definition. Five of 89 (5.6 %) of the mandibular fractures and 6 of 49 (12.2 %) zygomatic arch fractures had an associated posterolateral maxillary fracture. CONCLUSIONS: Segmental depressed fracture of the posterolateral maxillary sinus is relatively common, occurring in conjunction with other regional injuries. The authors hypothesize that it is due to a transient increase in pressure in the masticator space and is a separate entity from other fractures of the region that may occur concurrently.

Continuing versus Stopping Prestroke Antihypertensive Therapy in Acute Intracerebral Hemorrhage: A Subgroup Analysis of the Efficacy of Nitric Oxide in Stroke Trial.

BACKGROUND AND PURPOSE: More than 50% of patients with acute intracerebral hemorrhage (ICH) are taking antihypertensive drugs before ictus. Although antihypertensive therapy should be given long term for secondary prevention, whether to continue or stop such treatment during the acute phase of ICH remains unclear, a question that was addressed in the Efficacy of Nitric Oxide in Stroke (ENOS) trial. METHODS: ENOS was an international multicenter, prospective, randomized, blinded endpoint trial. Among 629 patients with ICH and systolic blood pressure between 140 and 220 mmHg, 246 patients who were taking antihypertensive drugs were assigned to continue (n = 119) or to stop (n = 127) taking drugs temporarily for 7 days. The primary outcome was the modified Rankin Score at 90 days. Secondary outcomes included death, length of stay in hospital, discharge destination, activities of daily living, mood, cognition, and quality of life. RESULTS: Blood pressure level (baseline 171/92 mmHg) fell in both groups but was significantly lower at 7 days in those patients assigned to continue antihypertensive drugs (difference 9.4/3.5 mmHg, P < .01). At 90 days, the primary outcome did not differ between the groups; the adjusted common odds ratio (OR) for worse outcome with continue versus stop drugs was .92 (95% confidence interval, .45-1.89; P = .83). There was no difference between the treatment groups for any secondary outcome measure, or rates of death or serious adverse events. CONCLUSIONS: Among patients with acute ICH, immediate continuation of antihypertensive drugs during the first week did not reduce death or major disability in comparison to stopping treatment temporarily.

Human metapneumovirus virus-like particles induce protective B and T cell responses in a mouse model.

UNLABELLED: Human metapneumovirus (HMPV) is a leading cause of respiratory disease in infants, children, and the elderly worldwide, yet no licensed vaccines exist. Live-attenuated vaccines present safety challenges, and protein subunit vaccines induce primarily antibody responses. Virus-like particles (VLPs) are an attractive alternative vaccine approach because of reduced safety concerns compared with live vaccines. We generated HMPV VLPs by expressing viral proteins in suspension-adapted human embryonic kidney epithelial (293-F) cells and found that the viral matrix (M) and fusion (F) proteins were sufficient to form VLPs. We previously reported that the VLPs resemble virus morphology and incorporate fusion-competent F protein (R. G. Cox, S. B. Livesay, M. Johnson, M. D. Ohi, and J. V. Williams, J. Virol. 86:12148-12160, 2012), which we hypothesized would elicit F-specific antibody and T cell responses. In this study, we tested whether VLP immunization could induce protective immunity to HMPV by using a mouse model. C57BL/6 mice were injected twice intraperitoneally with VLPs alone or with adjuvant and subsequently challenged with HMPV. Mice were euthanized 5 days postinfection, and virus titers, levels of neutralizing antibodies, and numbers of CD3(+) T cells were quantified. Mice immunized with VLPs mounted an F-specific antibody response and generated CD8(+) T cells recognizing an F protein-derived epitope. VLP immunization induced a neutralizing-antibody response that was enhanced by the addition of either TiterMax Gold or α-galactosylceramide adjuvant, though adjuvant reduced cellular immune responses. Two doses of VLPs conferred complete protection from HMPV replication in the lungs of mice and were not associated with a Th2-skewed cytokine response. These results suggest that nonreplicating VLPs are a promising vaccine candidate for HMPV. IMPORTANCE: Human metapneumovirus (HMPV) is a leading cause of acute respiratory infection in infants, children, and the elderly worldwide, yet no licensed vaccines exist. Live-attenuated vaccines present safety challenges, and protein subunit vaccines induce primarily antibody responses. Virus-like particles (VLPs) are an attractive alternative vaccine approach. We generated HMPV VLPs by expressing the viral matrix (M) and fusion (F) proteins in mammalian cells. We found that mice immunized with VLPs mounted an F-specific antibody response and generated CD8(+) T cells recognizing an F protein-derived epitope. VLP immunization induced a neutralizing-antibody response that was enhanced by the addition of either TiterMax Gold or α-galactosylceramide adjuvant. Two doses of VLPs conferred complete protection against HMPV replication in the lungs of mice and were not associated with a Th2-skewed cytokine response. These results suggest that nonreplicating VLPs are a promising vaccine candidate for HMPV.