Unpacking the paradoxical impact of ethical leadership on employees' pro-social rule-breaking behavior: The interplay of employees' psychological capital and moral identity.

This study delves into the complex dynamics of ethical leadership's influence on employees' pro-social rule-breaking behavior, taking into account the mediating role of psychological capital and the moderating effect of moral identity. Using data collected from nursing staff in Pakistani hospitals and analyzed through PLS SEM, the study yielded unexpected results. Contrary to the initial hypotheses, the findings reveal a positive relationship between ethical leadership and employees' pro-social rule-breaking behavior within organizational settings. Furthermore, the study identifies psychological capital as a key mediator in this relationship, while moral identity emerges as a crucial moderator. These results challenge the conventional perception of ethical leadership as an exclusively positive form of leadership and underscore its unintended consequences. Moreover, they underscore the significance of employees' psychological processes and individual differences in unraveling this paradoxical relationship. These results have the potential to reshape how organizations view ethical leadership and consider the unintended outcomes it may generate. Future research can build upon these findings to explore the boundaries and contextual factors that influence the effects of ethical leadership, ultimately contributing to a more comprehensive understanding of leadership dynamics in diverse organizational settings.

Systematic Review on the Worldwide Disparities in the Frequency and Results of Emergency Medical Services (EMS) and Response to Out-of-Hospital Cardiac Arrest (OHCA).

This systematic analysis aimed to analyze the key patterns and tendencies regarding bystander interventions, emergency medical service (EMS) systems, dispatcher support, regional and temporal differences, and the influence of national efforts on survival rates in out-of-hospital cardiac arrest (OHCA). The studies published between 2010 and 2024 examining outcomes of OHCA, interventions by bystanders, and variables linked to OHCA were included in this research. The inclusion process was done under Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), where publications (n = 24) from various geographical locations, including a wide range of research methodologies, were included for this research. The thematic analysis used for the data analysis shows that bystander cardiopulmonary resuscitation (CPR) enhances the chances of survival. The effectiveness of the EMS system, the assistance offered by dispatchers, and the inclusion of doctors in ambulance services are essential components in the management of OHCA. Regional and temporal variations highlight disparities in resuscitation protocols, emphasizing the need for adaptable approaches. Observations from statewide endeavors emphasize the impact of these activities in fostering a culture of prompt bystander intervention. This systematic review presents a comprehensive analysis of research conducted globally, providing a thorough insight into the variables that influence survival rates in instances of OHCA. The review recognizes the importance of bystander CPR and effective EMS services, while also bringing novel perspectives, such as gender disparities and geographical variations that contribute to the existing body of research. Despite possible variances in the studies and biases, the findings underscore the need for tailored therapies and ongoing research to optimize strategies for controlling OHCA and improving survival rates.

Development of Luminescent Biosensors for Calprotectin.

Calprotectin, a metal ion-binding protein complex, plays a crucial role in the innate immune system and has gained prominence as a biomarker for various intestinal and systemic inflammatory and infectious diseases, including inflammatory bowel disease (IBD) and tuberculosis (TB). Current clinical testing methods rely on enzyme-linked immunosorbent assays (ELISAs), limiting accessibility and convenience. In this study, we introduce the Fab-Enabled Split-luciferase Calprotectin Assay (FESCA), a novel quantitative method for calprotectin measurement. FESCA utilizes two new fragment antigen binding proteins (Fabs), CP16 and CP17, that bind to different epitopes of the calprotectin complex. These Fabs are fused with split NanoLuc luciferase fragments, enabling the reconstitution of active luciferase upon binding to calprotectin either in solution or in varied immobilized assay formats. FESCA's output luminescence can be measured with standard laboratory equipment as well as consumer-grade cell phone cameras. FESCA can detect physiologically relevant calprotectin levels across various sample types, including serum, plasma, and whole blood. Notably, FESCA can detect abnormally elevated native calprotectin from TB patients. In summary, FESCA presents a convenient, low-cost, and quantitative method for assessing calprotectin levels in various biological samples, with the potential to improve the diagnosis and monitoring of inflammatory diseases, especially in at-home or point-of-care settings.

24-Month Outcomes of Indirect Decompression Using a Minimally Invasive Interspinous Fixation Device versus Standard Open Direct Decompression for Lumbar Spinal Stenosis: A Prospective Comparison.

Purpose: An early-stage, multi-centre, prospective, randomised control trial with five-year follow-up was approved by Health Research Authority to compare the efficacy of a minimally invasive, laterally implanted interspinous fixation device (IFD) to open direct surgical decompression in treating lumbar spinal stenosis (LSS). Two-year results are presented. Patients and Methods: Forty-eight participants were randomly assigned to IFD or decompression. Primary study endpoints included changes from baseline at 8-weeks, 6, 12 and 24-months follow-ups for leg pain (visual analogue scale, VAS), back pain (VAS), disability (Oswestry Disability Index, ODI), LSS physical function (Zurich Claudication Questionnaire), distance walked in five minutes and number of repetitions of sitting-to-standing in one minute. Secondary study endpoints included patient and clinician global impression of change, adverse events, reoperations, operating parameters, and fusion rate. Results: Both treatment groups demonstrated statistically significant improvements in mean leg pain, back pain, ODI disability, LSS physical function, walking distance and sitting-to-standing repetitions compared to baseline over 24 months. Mean reduction of ODI from baseline levels was between 35% and 56% for IFD (p<0.002), and 49% to 55% for decompression (p<0.001) for all follow-up time points. Mean reduction of IFD group leg pain was between 57% and 78% for all time points (p<0.001), with 72% to 94% of participants having at least 30% reduction of leg pain from 8-weeks through 24-months. Walking distance for the IFD group increased from 66% to 94% and sitting-to-standing repetitions increased from 44% to 64% for all follow-up time points. Blood loss was 88% less in the IFD group (p=0.024) and operating time parameters strongly favoured IFD compared to decompression (p<0.001). An 89% fusion rate was assessed in a subset of IFD participants. There were no intraoperative device issues or re-operations in the IFD group, and only one healed and non-symptomatic spinous process fracture observed within 24 months. Conclusion: Despite a low number of participants in the IFD group, the study demonstrated successful two-year safety and clinical outcomes for the IFD with significant operation-related advantages compared to surgical decompression.

Vaccination with Mincle agonist UM-1098 and mycobacterial antigens induces protective Th1 and Th17 responses.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is one of the top infectious killers in the world. The only licensed vaccine against TB, Bacille Calmette-Guérin (BCG), provides variable protection against pulmonary TB, especially in adults. Hence, novel TB vaccine approaches are urgently needed. Both Th1 and Th17 responses are necessary for protection against TB, yet effective adjuvants and vaccine delivery systems for inducing robust Th1 and Th17 immunity are lacking. Herein we describe a synthetic Mincle agonist, UM-1098, and a silica nanoparticle delivery system that drives Th1/Th17 responses to Mtb antigens. Stimulation of human peripheral blood mononuclear cells (hPBMCs) with UM-1098 induced high levels of Th17 polarizing cytokines IL-6, IL-1ß, IL-23 as well as IL-12p70, IL-4 and TNF-α in vitro. PBMCs from both C57BL/6 and BALB/c mice responded with a similar cytokine pattern in vitro and in vivo. Importantly, intramuscular (I.M.) vaccination with UM-1098-adjuvanted TB antigen M72 resulted in significantly higher antigen-specific IFN-γ and IL-17A levels in C57BL/6 wt mice than Mincle KO mice. Vaccination of C57BL/6 wt mice with immunodominant Mtb antigens ESAT6/Ag85B or M72 resulted in predominantly Th1 and Th17 responses and induced antigen-specific serum antibodies. Notably, in a virulent Mtb challenge model, vaccination with UM-1098 adjuvanted ESAT6/Ag85B or M72 significantly reduced lung bacterial burden when compared with unvaccinated mice and protection occurred in the absence of pulmonary inflammation. These data demonstrate that the synthetic Mincle agonist UM-1098 induces strong Th1 and Th17 immunity after vaccination with Mtb antigens and provides protection against Mtb infection in mice.

Phytochemical analysis, antioxidant, acetylcholinesterase, and α-amylase inhibitors from extract.

OBJECTIVE: To investigate the effects of Hippeastrum hybridum (HH) as a free radical scavenger, and an inhibitor of the two enzymes i-e Alpha-amylase (α-amylase) and acetylcholinesterase (AChE). METHODS: In this study, HH plant was preliminary analyzed for phytochemical screening and then tested for its antioxidant, anti-α-amylase, and anti-AChE efficiency via standard procedures. RESULTS: Phytochemical analysis shows the existence of different compounds; while Coumarins and quinones were absent. The total phenolic, flavonoid, and tannins content were found to be (78.52 ± 0.69) mg GAE/g, (2.01 ± 0.04) mg RUE/g, and (58.12 ± 0.23) mg TAE/g of plant extract respectively. 28.02% ± 0.02% alkaloid and 2.02% ± 0.05% saponins were present in the HH extract. The HH extract showed the anti-oxidant property with IC50 (50% inhibition) of (151.01 ± 0.13) (HH), (79.01 ± 0.04) (Ascorbic acid) for ferric reducing, (91.48 ± 0.13) (HH), (48.02 ± 0.11) (Ascorbic acid) against Ammonium molybdenum, (156.02 ± 0.31) (HH), (52.38 ± 0.21) (Ascorbic acid) against DPPH, 136.01 ± 0.21 (HH), 52.02± 0.31 (Ascorbic acid) against H2O2, and 154.12 ± 0.03 (HH), (40.05 ± 0.15) (Ascorbic acid) µg/mL against ABTS respectively. Statistical analysis indicated that HH caused a competitive type of inhibition of α-amylase (Vmax remained constant and Km increases from 10.65 to 84.37%) while Glucophage caused the un-competitive type of inhibition i-e both Km and Vmax decreased from 40.49 to 69.15% and 38.86 to 69.61% respectively. The Ki, (inhibition constant); KI, (dissociation constant), Km, (Michaelis-Menten constant), and IC50 were found to be 62, 364, 68.1, and 38.08 ± 0.22 for HH and 12, 101.05, 195, 34.01 ± 0.21 for Glucophage. Similarly, HH causes an anon-competitive type of inhibition of AChE i-e Km remains constant while Vmax decreases from 60.5% to 74.1%. The calculated Ki, KI, Km, and IC50 were found to be 32, 36.2, 0.05, and 18.117 ± 0.018. CONCLUSION: From the current results, it is concluded that HH extract contains bioactive compounds, and could be a good alternative to controlling oxidants, Alzheimer's and Type-II diabetic diseases.

Phospholipase C epsilon-1 (PLCƐ1) mediates macrophage activation and protection against tuberculosis.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infects up to a quarter of the world's population. Although immune responses can control Mtb infection, 5%-10% of infected individuals can progress to active TB disease (progressors). A myriad of host factors regulate disease progression in TB and a better understanding of immune correlates of protection and disease is pivotal for the development of new therapeutics. Comparison of human whole blood transcriptomic metadata with that of macaque TB progressors and Mtb-infected diversity outbred mice (DO) led to the identification of differentially regulated gene (DEG) signatures, associated with TB progression or control. The current study assessed the function of Phospholipase C epsilon (PLCƐ1), the top downregulated gene across species in TB progressors, using a gene-specific knockout mouse model of Mtb infection and in vitro Mtb-infected bone marrow-derived macrophages. PLCƐ1 gene expression was downregulated in TB progressors across species. PLCε1 deficiency in the mouse model resulted in increased susceptibility to Mtb infection, coincident accumulation of lung myeloid cells, and reduced ability to mount antibacterial responses. However, PLCε1 was not required for the activation and accumulation of T cells in mice. Our results suggest an important early role for PLCƐ1 in shaping innate immune response to TB and may represent a putative target for host-directed therapy.

Nuclear Factor κB Signaling Deficiency in CD11c-Expressing Phagocytes Mediates Early Inflammatory Responses and Enhances Mycobacterium tuberculosis Control.

Early innate immune responses play an important role in determining the protective outcome of Mycobacterium tuberculosis (Mtb) infection. Nuclear factor κB (NF-κB) signaling in immune cells regulates the expression of key downstream effector molecules that mount early antimycobacterial responses. Using conditional knockout mice, we studied the effect of abrogation of NF-κB signaling in different myeloid cell types and its impact on Mtb infection. Our results show that the absence of IKK2-mediated signaling in all myeloid cells resulted in increased susceptibility to Mtb infection. In contrast, the absence of IKK2-mediated signaling in CD11c+ myeloid cells induced early proinflammatory cytokine responses, enhanced the recruitment of myeloid cells, and mediated early resistance to Mtb. Abrogation of IKK2 in MRP8-expressing neutrophils did not affect disease pathology or Mtb control. Thus, we describe an early immunoregulatory role for NF-κB signaling in CD11c-expressing phagocytes and a later protective role for NF-κB in LysM-expressing cells during Mtb infection.

Lung type 3 innate lymphoid cells respond early following Mycobacterium tuberculosis infection.

Tuberculosis is the leading cause of death due to an infectious disease worldwide. Innate lymphoid type 3 cells (ILC3s) mediate early protection during Mycobacterium tuberculosis (Mtb) infection. However, the early signaling mechanisms that govern ILC3 activation or recruitment within the lung during Mtb infection are unclear. scRNA-seq analysis of Mtb-infected mouse lung innate lymphoid cells (ILCs) has revealed the presence of different clusters of ILC populations, suggesting heterogeneity. Using mouse models, we show that during Mtb infection, interleukin-1 receptor (IL-1R) signaling on epithelial cells drives ILC3 expansion and regulates ILC3 accumulation in the lung. Furthermore, our data revealed that C-X-C motif chemokine receptor 5 (CXCR5) signaling plays a crucial role in ILC3 recruitment from periphery during Mtb infection. Our study thus establishes the early responses that drive ILC3 accumulation during Mtb infection and points to ILC3s as a potential vaccine target. IMPORTANCE: Tuberculosis is a leading cause of death due to a single infectious agent accounting for 1.6 million deaths each year. In our study, we determined the role of type 3 innate lymphoid cells in early immune events necessary for achieving protection during Mtb infection. Our study reveals distinct clusters of ILC2, ILC3, and ILC3/ILC1-like cells in Mtb infection. Moreover, our study reveal that IL-1R signaling on lung type 2 epithelial cells plays a key role in lung ILC3 accumulation during Mtb infection. CXCR5 on ILC3s is involved in ILC3 homing from periphery during Mtb infection. Thus, our study provides novel insights into the early immune mechanisms governed by innate lymphoid cells that can be targeted for potential vaccine-induced protection.

Saponin TQL1055 adjuvant-containing vaccine confers protection upon Mycobacterium tuberculosis challenge in mice.

Tuberculosis (TB), caused by the intracellular pathogen Mycobacterium tuberculosis (Mtb), affects the lungs of infected individuals (pulmonary TB) but can also affect other sites (extrapulmonary TB). The only licensed vaccine Mycobacterium bovis bacillus Calmette-Guerin (BCG) protects infants and young children but exhibits variable efficacy in protecting against adult pulmonary TB. Poor compliance and prolonged treatment regimens associated with the use of chemotherapy has contributed to the development of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mtb. Thus, there is an urgent need for the design of more effective vaccines against TB. The development of safe and novel adjuvants for human use is critical. In this study, we demonstrate that saponin-based TQL1055 adjuvant when formulated with a TLR4 agonist (PHAD) and Mtb specific immunodominant antigens (ESAT-6 and Ag85B) and delivered intramuscularly in mice, the SA-TB vaccine induced potent lung immune responses. Additionally, the SA-TB vaccine conferred significant protection against Mtb infection, comparable with levels induced by BCG. These findings support the development of a SA-TB vaccine comprising TQL1055, as a novel, safe and effective TB vaccine for potential use in humans.

Beyond the universal perception: Unveiling the paradoxical impact of ethical leadership on employees' unethical pro-organizational behavior.

Ethical leadership, widely recognized as a positive leadership style, has shown inconsistent relationships with employees' unethical pro-organizational behavior in the workplace. This study draws on the social cognitive theory to investigate the paradoxical impact of ethical leadership on employees' unethical pro-organizational behavior. It also examines the mediating role of employees' psychological empowerment and the moderating effect of moral identity. The study collects data from 515 nursing staff working in public and private hospitals in Pakistan at three different time intervals, and analyzed using PLS SEM. Contrary to the previous studies and our initial hypothesis, the findings reveal a positive relationship between ethical leadership and employees' unethical pro-organizational behavior. Additionally, the study demonstrates that employees' psychological empowerment positively mediates the relationship between ethical leadership and employees' unethical pro-organizational behavior. This underscores the significance of employees' psychological processes. Furthermore, the relationship between ethical leadership and employees' psychological empowerment is moderated by employees' moral identity. This highlights the role of the individual differences in shaping employees' behavior within the workplace. Overall, these results challenge the universal perception of ethical leadership as a positive form of leadership, shedding light on the unintended consequences and paradoxical impact it can have in organizations.

Revolutionizing Nanotechnology with Filago desertorum Extracts: Biogenic Synthesis of Silver Nanoparticles Exhibiting Potent Antioxidant and Antibacterial Activities.

In this study, we described the environmentally friendly biosynthesis of silver nanoparticles (AgNPs) utilizing ethanolic extract of Filago desertorum (F. desertorum) as a capping and reducing agent. We also looked at the antioxidant and antibacterial capacities of AgNPs. In order to determine the size, shape, and crystallinity of the created AgNPs, the current project was designed to produce AgNPs utilizing the crude extract of the F. desertorum. The effectiveness of the project was evaluated by UV-visible spectrophotometry, Fourier transform infrared spectroscopy, scanning electron microscopy, and X-ray diffraction. AgNPs are monodispersed and spherical and have 50 nm average particle diameters, as determined using Image J software calculations and SEM observation. Four significant peaks from an XRD study, located at 38.46, 44.63, 64.81, and 77.74 nm, were used to calculate the average crystalline size of AgNPs which was reported to be 15 nm. In the crude extract of F. desertorum, it is possible to see the functional group peaks of a number of substances that are essential for bioreduction and the stability of the AgNPs. Antibacterial and antioxidant properties of AgNPs in vitro (DPPH, ABTS, H2O2, phosphomolybdenum, and ferric reducing power) were examined using conventional methods. The AgNPs showed maximum DPPH (72.51% with IC50 = 144.61 µg/mL), ABTS (75.24% with IC50 = 131.21 µg/mL), hydrogen peroxide (73.33% with IC50 = 115.05 µg/mL), phosphomolybdenum activity (73.43% with IC50 = 75.25 µg/mL), and observing reducing power (0.25) at a concentration of 250 g/mL. Inhibition by the AgNPs against the bacterial strain Staphylococcus aureus was greatest (12 mm). According to the current findings, AgNPs produced by F. desertorum have the highest potential for free radical scavenging and antibacterial activity, which can result in antioxidant and antibiotic agents.

Mycobacterium tuberculosis carrying the rifampicin drug-resistance-conferring rpoB mutation H445Y is associated with suppressed immunity through type I interferons.

IMPORTANCE: This study highlights the impact of specific rifampicin-resistance-conferring mutations on the host immune response to Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB). Clinical reports have previously suggested that multi-drug-resistant) TB patients exhibit altered peripheral immune responses as compared with their drug-sensitive TB counterparts. The murine model of infection with Mtb strains carrying drug-resistance-conferring mutations recapitulated these findings and allowed us to mechanistically interrogate the pathways responsible for driving the divergent immune responses. Our findings underscore the need for greater investigation into bacterial heterogeneity to better appreciate the diversity in host-pathogen interactions during TB disease.

Mycobacterium tuberculosis infection drives differential responses in the bone marrow hematopoietic stem and progenitor cells.

Hematopoietic stem and progenitor cells (HSPCs) play a vital role in the host response to infection through the rapid and robust production of mature immune cells. These HSPC responses can be influenced, directly and indirectly, by pathogens as well. Infection with Mycobacterium tuberculosis (Mtb) can drive lymphopoiesis through modulation of type I interferon (IFN) signaling. We have previously found that the presence of a drug resistance (DR)-conferring mutation in Mtb drives altered host-pathogen interactions and heightened type I IFN production in vitro. But the impacts of this DR mutation on in vivo host responses to Mtb infection, particularly the hematopoietic compartment, remain unexplored. Using a mouse model, we show that, while drug-sensitive Mtb infection induces expansion of HSPC subsets and a skew toward lymphopoiesis, DR Mtb infection fails to induce an expansion of these subsets and an accumulation of mature granulocytes in the bone marrow. Using single-cell RNA sequencing, we show that the HSCs from DR Mtb-infected mice fail to upregulate pathways related to cytokine signaling across all profiled HSC subsets. Collectively, our studies report a novel finding of a chronic infection that fails to induce a potent hematopoietic response that can be further investigated to understand pathogen-host interaction at the level of hematopoiesis.

Analysis of the Performance of a Gel Actuator Made of Plasticized Polyvinyl Chloride/Carboxylated Cellulose Nanocrystals.

Recently, polyvinyl chloride (PVC) gel materials appeared promising for developing actuators, artificial muscles, and sensors. However, their energized response time and recovery limitations restrict their broader applications. Herein, a novel soft composite gel was prepared by mixing functionalized carboxylated cellulose nanocrystals (CCNs) and plasticized PVC. The surface morphology of the plasticized PVC/CCNs composite gel was characterized by scanning electronic microscopy (SEM). The prepared PVC/CCNs gel composites have increased polarity and electrical actuation with a fast response time. Experimental results demonstrated good response characteristics within the actuator model with a multilayer electrode structure when stimulated with a specified DC voltage (1000 V), with deformation of approximately 36.7%. Moreover, this PVC/CCNs gel has excellent tensile elongation, and the elongation at break of the PVC/CCNs gel is greater than the elongation at break of the pure PVC gel under the same thickness conditions. However, these PVC/CCNs composite gels showed excellent properties and development potential and are directed for broad applications in actuators, soft-robotics, and biomedical applications.

A review article on the dosimetry in intraluminal HDR brachytherapy of lung carcinoma.

Lung cancer is one of the most common cancers in the world. Intraluminal brachytherapy (BT) is one of the most adopted treatment modalities for lung malignancies with Ir-192 source in radiotherapy. In intraluminal BT, treatment delivery is required to be very accurate and precise with respect to the plan created in the treatment planning system (TPS). The BT dosimetry is necessary for better treatment outcomes. Therefore in this review article, some relevant studies were identified and analyzed for dosimetric outcomes in intraluminal BT in lung malignancies. The dosimetry in BT for plan verification is not presently in practice, which needs to be performed to check the variation between the planned and measured doses. The necessary dosimetric work done by the various researchers in intraluminal BT such as the Monte Carlo CYLTRAN code was used to calculate and measure the dose rate in any medium. Anthropomorphic phantom was used to measure doses at some distance from the source with Thermo luminescence dosimeters (TLDs). The dosimetric influence of air passage in the bronchus was evaluated with the GEANT4 Monte Carlo method. A pinpoint chamber was used to measure and quantify the impact of inhomogeneity in wax phantom for the Ir-192 source. The Gafchromic films and Monte Carlo methods were used to find the phantom and heterogeneities, which were found to underestimate the dose for the lungs and overestimated for the bones in TPS. The exact tool to quantify the variation in planned and delivered doses should be cost-effective and easy to use possibly with tissue equivalent phantoms and Gafchromic films in lung malignancies treatment.

Poly(ADP-ribose) polymerase 9 mediates early protection against Mycobacterium tuberculosis infection by regulating type I IFN production.

The ADP ribosyltransferases (PARPs 1-17) regulate diverse cellular processes, including DNA damage repair. PARPs are classified on the basis of their ability to catalyze poly-ADP-ribosylation (PARylation) or mono-ADP-ribosylation (MARylation). Although PARP9 mRNA expression is significantly increased in progressive tuberculosis (TB) in humans, its participation in host immunity to TB is unknown. Here, we show that PARP9 mRNA encoding the MARylating PARP9 enzyme was upregulated during TB in humans and mice and provide evidence of a critical modulatory role for PARP9 in DNA damage, cyclic GMP-AMP synthase (cGAS) expression, and type I IFN production during TB. Thus, Parp9-deficient mice were susceptible to Mycobacterium tuberculosis infection and exhibited increased TB disease, cGAS and 2'3'-cyclic GMP-AMP (cGAMP) expression, and type I IFN production, along with upregulation of complement and coagulation pathways. Enhanced M. tuberculosis susceptibility is type I IFN dependent, as blockade of IFN α receptor (IFNAR) signaling reversed the enhanced susceptibility of Parp9-/- mice. Thus, in sharp contrast to PARP9 enhancement of type I IFN production in viral infections, this member of the MAR family plays a protective role by limiting type I IFN responses during TB.

Antigen-specific B cells direct T follicular-like helper cells into lymphoid follicles to mediate Mycobacterium tuberculosis control.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a global cause of death. Granuloma-associated lymphoid tissue (GrALT) correlates with protection during TB, but the mechanisms of protection are not understood. During TB, the transcription factor IRF4 in T cells but not B cells is required for the generation of the TH1 and TH17 subsets of helper T cells and follicular helper T (TFH)-like cellular responses. A population of IRF4+ T cells coexpress the transcription factor BCL6 during Mtb infection, and deletion of Bcl6 (Bcl6fl/fl) in CD4+ T cells (CD4cre) resulted in reduction of TFH-like cells, impaired localization within GrALT and increased Mtb burden. In contrast, the absence of germinal center B cells, MHC class II expression on B cells, antibody-producing plasma cells or interleukin-10-expressing B cells, did not increase Mtb susceptibility. Indeed, antigen-specific B cells enhance cytokine production and strategically localize TFH-like cells within GrALT via interactions between programmed cell death 1 (PD-1) and its ligand PD-L1 and mediate Mtb control in both mice and macaques.