Immune Effector Research Articles

Targeting uPAR with an antibody-drug conjugate suppresses tumor growth and reshapes the immune landscape in pancreatic cancer models.

Antibody-drug conjugates (ADCs) hold promise to advance targeted therapy of pancreatic ductal adenocarcinoma (PDAC), where the desmoplastic tumor stroma challenges effective treatment. Here, we explored the urokinase plasminogen activator receptor (uPAR) as a candidate ADC target in PDAC, harnessing its massive tumoral and stromal expression in this stroma-dense tumor. We generated a site-specific ADC offering high-affinity, cross-species reactivity, and efficient internalization of the anti-uPAR monoclonal antibody, FL1, carrying a potent anthracycline derivative (PNU-158692). In vitro, FL1-PNU exhibited potent and specific cytotoxicity against uPAR-expressing PDAC cell lines, stromal and immune cells, and bystander killing of uPAR-negative cells. In vivo, the ADC induced remission or sustained tumor regression and extended survival in xenograft models. In syngeneic orthotopic models, the antitumor effect promoted immunomodulation by enhancing infiltrating immune effectors and decreasing immunosuppressive cells. This study lays grounds for further exploring FL1-PNU as a putative clinical ADC candidate, potentially providing a promising therapeutic avenue for PDAC as a monotherapy or in combinatorial regimens.

Role of procalcitonin, C reactive protein and ferritin in cytokine release syndrome after CAR T-cell therapy in children and young adults

ABSTRACT Purpose Chimeric antigen receptor (CAR) T-cell CD19 therapy has changed the treatment paradigm for patients with relapsed/refractory B-cell acute lymphoblastic leukemia. It is frequently associated with potentially severe toxicities: cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and admission to PICU is often required. Some biomarkers seem to correlate with CRS severity. Our goal is to elucidate the role of procalcitonin (PCT), C-reactive protein (CRP) and ferritin in the context of CRS following CAR T-cell infusion to predict its severity and PICU admission. Methods Prospective observational study (2016-2022) in children and young adult who received CAR T-cell therapy (Tisagenlecleucel/ARI-0001). We collected epidemiologic data, specific CAR T-cell toxicities, PICU admission, biomarker results (procalcitonin, CRP and ferritin), length of stay and mortality. Biomarkers were analyzed considering two values: the highest value during ward admission, and the highest overall value including PICU admission. Results Seventy-seven patients were included. Median age at infusion was 9.1 years (IQR 6-13), 49.4% were females. Before CAR T-cell infusion, the median bone marrow blast was 9% (IQR 0-59). The most frequent toxicity was CRS in 62 patients (80.5%), it was severe in 18 cases (23.4%). Fourteen patients (18.1%) had ICANS. Thirty-one patients (40.3%) required admission to the PICU. PCT and ferritin were higher in patients admitted to PICU (PCT 0.8 ng/ml vs 0.15 ng/ml, p < 0.001, ferritin 5490 vs. 2900 ug/l, p < 0.019). The proposed cut-off for PCT to predict admission to PICU is 0.55 ng/mL, presenting a sensitivity of 67.7% and a specificity of 86.7%. The maximum value of the three biomarkers was higher in those who presented any primary outcome: development of a severe CRS, the need for admission to PICU, and in-hospital mortality. Biomarkers were higher in those who needed inotropic or respiratory support. Conclusions PCT levels increase after CAR-T cell therapy in the setting of systemic inflammation and could be a predictor of PICU admission and evolution to death. Further research studying its role in the context of CRS and the differential diagnosis between infection and CRS is needed to better understand the biology of this biomarker and to define its value in clinical practice.

Spatial Kinetic Modeling of Crowd Evacuation: Coupling Social Behavior and Infectious Disease Contagion

This paper introduces a kinetic model of crowd evacuation from a bounded domain, integrating social behavior and contagion dynamics. The model describes the spatial movement of individuals in a crowd, taking into account interactions with other people and the geometry of the environment. Interactions between healthy and infectious individuals can lead to disease transmission and are considered. The approach is grounded in the kinetic theory of active particles, where the activity variable represents both the infectious disease status of individuals (e.g., susceptible, infected) and the psychological state of pedestrians, including contagion awareness. Varying awareness levels influence individual behavior, leading to more cautious movement patterns, potentially reducing the overall infection rate. The performance of the model is evaluated through a series of numerical simulations. Different scenarios are examined to investigate the impact of awareness levels on pedestrian behavior, infectious disease spread, and evacuation times. Additionally, the effects of population immunization and individual contagion awareness are assessed to determine the most effective strategy for reducing infections. The results provide valuable insights into targeted strategies to mitigate contagion.

Multiple Myeloma Cells Shift the Fate of Cytolytic ILC2s Towards TIGIT-Mediated Cell Death

Background: Growing evidence attests to the multifaceted roles of group 2 innate lymphoid cells (ILC2s) in cancer immunity. They exhibit either pro- or anticancer activity depending on tumor type but their function in Multiple Myeloma (MM) is still not elucidated. Methods: The bone marrow (BM) and peripheral blood (PB) of patients (pts) with MM or precancerous conditions were collected, and specific properties of ILC2 subsets were assessed by flow cytometry. Results: By dissecting ILC2s according to c-Kit marker, we observed that NKp30 and NKG2D were mainly confined to c-Kithi ILC2s, while levels of DNAM-1 was significantly higher in fully mature c-Kitlo cells. Among the total MM-associated ILC2s (MM-ILC2s), we observed a significant increase in c-the Kitlo subset, but the expression of DNAM-1 in these cells was significantly reduced, especially in BM. Interestingly, MM-ILC2s from PB expressed granzyme B (GZMB), but its expression was impaired in BM-ILC2s. Accordingly, MM cells were susceptible to killing by MM-ILC2s derived from PB while eluding ILC2 surveillance in BM. Indeed, in MM-ILC2s derived from BM, the downregulation of DNAM-1 is accompanied by the upregulation of TIGIT, which mediate cell death in ILC2s upon recognition of the cognate ligands expressed by MM cells. These ILC2 changes appeared in clinical precursor conditions and eventually accumulated with disease progression. Conclusions: MM-ILC2s can act as cytolytic immune effectors that are fully competent in PB. However, MM cells shift ILC2 fate towards cell death in BM via the upregulation of TIGIT, thereby representing a potential therapeutic target to restore ILC2 antitumor activity.

A phase 1 trial of prizloncabtagene autoleucel, a CD19/CD20 CAR T-cell therapy for relapsed/refractory B-cell non-Hodgkin lymphoma.

Prizloncabtagene autoleucel (prizlon-cel), a novel bispecific chimeric antigen receptor (CAR) T-cell, targets and eliminates CD19/CD20 positive tumor cells. This phase 1, open-label study investigated the safety and efficacy of prizlon-cel in patients with relapsed/refractory B-cell non-Hodgkin Lymphoma (r/r B-NHL). Patients with CD19 and/or CD20-positive r/r B-NHL received a 3-day lymphodepletion (cyclophosphamide: 300 mg/m2/d; fludarabine: 30 mg/m2/d) followed by an intravenous dose of prizlon-cel. The primary endpoints were dose-limiting toxicity (DLT) and incidence and severity of treatment-emergent adverse events (TEAEs). Secondary endpoints included overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Of the 48 patients infused prizlon-cel, 44 had large B-cell lymphoma (LBCL). No patient experienced DLT. Cytokine release syndrome occurred in 93.8% of patients, with only one case of grade 3. Immune effector cell-associated neurotoxicity syndrome occurred in 6.3% of patients, with no grade 3 or higher events. The most common grade 3 or higher TEAEs were neutropenia (83.3%) and leukopenia (50%). The ORR and complete response (CR) rates in all patients were 91.5% and 85.1%, respectively, and in LBCL patients, ORR was 90.7% with 86.0% CR. With median follow up of 30.0 months, median DOR, PFS, and OS were all not reached. The Kaplan-Meier estimate of 2-year DOR, PFS and OS rates were 66.0%, 62.6%, and 76.5%, respectively. Prizlon-cel showed a favorable safety profile and a high and durable response in patients with r/r B-NHL, suggesting a promising treatment option for patients with r/r B-NHL. (ClinicalTrials.gov number: NCT04317885, NCT04655677, NCT04696432, NCT04693676).

DAMPs, PAMPs, NLRs, RIGs, CLRs and TLRs - Understanding the Alphabet Soup in the Context of Bone Biology.

The purpose of this review is to summarize the current understanding of cell-autonomous innate immune pathways that contribute to bone homeostasis and disease. Germ-line encoded pattern recognition receptors (PRRs) are the first line of defense against danger and infections. In the bone microenvironment, PRRs and downstream signaling pathways, that mount immune defense, interface intimately with the core cellular processes in bone cells to alter bone formation and resorption. The role of PRR engagement on bone remodeling has been best described as a result of activated macrophages secreting effector molecules that reshape the characteristics of bone-resident cells. However, it is being increasingly recognized that local bone resident-cells like osteoclasts and osteoblasts possess an arsenal of PRRs. The engagement of these PRRs by stimuli in the bone niche can drive cell-autonomous (aka cell-intrinsic) responses that, in turn, impact bone-remodeling dramatically, irrespective of immune cell effectors. Indeed, this vital role for cell-autonomous innate immune responses is evident in how reduced PRR activity within osteoclast progenitors correlates with their reduced differentiation and abnormal bone remodeling. Further, cell-intrinsic PRR activity has now been shown to influence the behavior of osteoblasts, osteocytes and other local immune/non-immune cell populations. However, distinct PRR families have varying impact on bone homeostasis and inflammation, emphasizing the importance of investigating these different nodes of innate immune signaling in bone cells to better identify how they synergistically and/or antagonistically regulate bone remodeling in the course of an immune response. Innate immune sensing within bone resident cells is a critical determinant for bone remodeling in health and disease.

Case report: The case of T-cell acute lymphoblastic leukemia treated with chemotherapy followed by anti-CD7 CAR-T cells using retroviral vector

CD7-targeted chimeric antigen receptor-T (CAR-T) cell therapy has shown great promise in the treatment of relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL). In this study, we reported a case of a 34-year-old male patient with T-ALL who finally developed multi-line drug resistance and refractoriness after multiple lines of high-intensity chemotherapy. After physician evaluation, this patient received allogeneic hematopoietic stem cell transplantation (allo-HSCT). Then, The patient remained in complete remission (CR) for four months before a relapse with 26.64% chimerism rate, so he was treated with allogeneic anti-CD7 CAR-T cells after chemotherapy reducing the tumor burden. The CAR-T product was a novel anti-CD7 CAR-T based on retroviral vectors (RV). After infusion, the patient achieved CR within 1 month after anti-CD7 CAR-T infusion and the remission has been ongoing for 9 months to date. Cytokine release syndrome (CRS) 1 was experienced while no immune effector cell-associated neurotoxicity syndrome (ICANS) was found. In addition, CAR copy number peaked at 350, 758 copies/μg on day 6. This case report of clinical treatment of T-ALL with anti-CD7 CAR-T cells prepared using a retroviral vector without gene editing and combined with chemotherapy, which demonstrated that the RV-based anti-CD7 CAR-T cells had good therapeutic effect and high safety in triple-refractory T-ALL patients.

Neo-BCV: A Novel Bacterial Liquid Complex Vaccine for Enhancing Dendritic Cell-Mediated Immune Responses Against Lung Cancer

Background: In the past decade, immunotherapy has become a major choice for the treatment of lung cancer, yet its therapeutic efficacy is still relatively limited due to the various immune escape mechanisms of tumors. Based on this, we introduce Neo-BCV, a novel bacterial composite vaccine designed to enhance immune responses against lung cancer. Methods: We investigated the immune enhancing effect of Neo-BCV through in vivo and in vitro experiments, including flow cytometry, RNA-seq, and Western blot. Results: We have demonstrated that Neo-BCV can promote Dendritic cells (DCs) maturation and induce DCs differentiation into pro-inflammatory subgroups, significantly enhancing cytotoxic T lymphocyte (CTL)-mediated anti-tumor responses. Transcriptome sequencing revealed that Neo-BCV exerts its effects by specifically inhibiting the JAK2-STAT3 signaling pathway, a crucial regulator of cancer progression, metabolism, and inflammation. Moreover, Neo-BCV significantly improved the immune microenvironment in both tumor and spleen tissues without inducing notable toxic effects in major organs. Conclusions: These findings highlight Neo-BCV’s potential as a safe and effective therapeutic strategy, offering a novel avenue for clinical translation in lung cancer immunotherapy.

Hemolymph microbiota and immune effectors’ expressions driven by geographical rearing acclimation of the aquacultured Penaeus stylirostris

BackgroundIn holobiont, microbiota is known to play a central role on the health and immunity of its host. Then, understanding the microbiota, its dynamic according to the environmental conditions and its link to the immunity would help to react to potential dysbiosis of aquacultured species. While the gut microbiota is highly studied, in marine invertebrates the hemolymph microbiota is often set aside even if it remains an important actor of the hemolymph homeostasis. Indeed, the hemolymph harbors the factors involved in the animal homeostasis that interacts with the microbiota, the immunity. In the Southwest Pacific, the high economical valued shrimp Penaeus stylirostris is reared in two contrasted sites, in New Caledonia (NC) and in French Polynesia (FP).ResultsWe characterized the active microbiota inhabiting the hemolymph of shrimps while considering its stability during two seasons and at a one-month interval and evidenced an important microbial variability between the shrimps according to the rearing conditions and the sites. We highlighted specific biomarkers along with a common core microbiota composed of 6 ASVs. Putative microbial functions were mostly associated with bacterial competition, infections and metabolism in NC, while they were highly associated with the cell metabolism in FP suggesting a rearing site discrimination. Differential relative expression of immune effectors measured in the hemolymph of two shrimp populations from NC and FP, exhibited higher level of expression in NC compared to FP. In addition, differential relative expression of immune effectors was correlated to bacterial biomarkers based on their geographical location.ConclusionsOur data suggest that, in Pacific shrimps, both the microbiota and the expression of the immune effectors could have undergone differential immunostimulation according to the rearing site as well as a geographical adaptative divergence of the shrimps as an holobiont, to their rearing sites. Further, the identification of proxies such as the core microbiota and site biomarkers, could be used to guide future actions to monitor the bacterial microbiota and thus preserve the productions.

Protocol for assessing immune-target cell interactions using a single-cell cytotoxicity assay.

Standard flow cytometry-based assays can determine the cytotoxicity of immune effector cells, but it is challenging to monitor the dynamic processes of cytotoxicity. Here, we present a protocol for continuous observation of natural killer (NK) cell-mediated cytotoxicity with microwell arrays using an automated microscope. We describe steps for isolating and labeling primary NK cells, loading cells onto microwell arrays, monitoring target wells, and image analysis. This protocol facilitates observation of the dynamics of immune-target cell interactions at the single-cell level. For complete details on the use and execution of this protocol, please refer to Lietal.1.

Induction of macrophage efferocytosis in pancreatic cancer via PI3Kγ inhibition and radiotherapy promotes tumour control

BackgroundThe immune suppression mechanisms in pancreatic ductal adenocarcinoma (PDAC) remain unknown, but preclinical studies have implicated macrophage-mediated immune tolerance. Hence, pathways that regulate macrophage phenotype are of strategic interest, with...

Effects of Red Clover Isoflavones on Growth Performance, Immune Function, and Cecal Microflora of Mice

Isoflavone components extracted from red clover have anti-inflammatory, antioxidant and immune boosting effects. We hypothesize that red clover isoflavones (RCIs) achieve health-promoting effects via altering the gut microbiota. A total of 48 mice (20 ± 2 g) were randomly divided into a control group, low-dose group (0.05% RCIs in feed), middle-dose group (0.1% RCIs in feed), and high-dose group (0.2% RCIs in feed) with 12 mice per group. The feeding period was 20 d. The results showed that RCIs can increase the daily gain and decrease the ratio of feed to gain in mice. The organ indexes and blood biochemical indexes of the mice in each RCI group were in the normal range, indicating that RCIs do not damage liver or kidney function. RCI supplementation increased serum immunity and altered the microbial community structure in the cecum of the mice. RCIs can increase the diversity of beneficial bacteria such as Bacteroidaceae, Muribaculaceae, and Akkermansiaceae, and reduced the pathogenic Staphylococcaceae. Therefore, supplementing the diet with RCIs results in improved growth performance and notable alterations in the cecal microbiota in mice, and has potential applications as a feed additive to improve livestock production.

Potential role of TRAF2 in pulmonary hypertension in broiler chickens and preparation and specificity analysis of its polyclonal antibody.

Due to the lack of specific antibody anti-chicken tumor necrosis factor receptor-associated factor 2 (TRAF2), it is difficult to further explore the role of TRAF2 in pulmonary artery remodeling in pulmonary hypertension(PH) in broilers. In this experiment, we prepared a polyclonal antibody to TRAF2 by constructing a TRAF2 recombinant protein prokaryotic expression vector and analyzed the expression of TRAF2 in in vivo and in vitro models of pulmonary hypertension in broiler chickens and the effect of TRAF2 on the activity and apoptosis of PASMCs. The results showed that after immunization with TRAF2 recombinant protein we obtained high titers of polyclonal antibodies, and astragalus polysaccharide as an immune adjuvant could enhance the effect of immunization. Antibody specificity showed that the TRAF2 polyclonal antibody specifically bound to TRAF2 protein in chickens and ducks but weakly to TRAF2 protein in rabbits, mice and goats.TRAF2 was significantly upregulated in an in vivo and in vitro model of PH in broilers. Knockdown of TRAF2 inhibited the activity of PASMCs and induced apoptosis in PASMCs. Our study lays the foundation for further research on the pathomechanism of PH in broiler chickens and provides new targets for its prevention and drug development.

High-dose intravenous immunoglobulin may be an efficient treatment option for patients with late-onset high-grade immune effector cell-associated hematotoxicity refractory to standard therapies.

Not available.

Acidic pH can attenuate immune killing through inactivation of perforin.

Cytotoxic lymphocytes are crucial to our immune system, primarily eliminating virus-infected or cancerous cells via perforin/granzyme killing. Perforin forms transmembrane pores in the plasma membrane, allowing granzymes to enter the target cell cytosol and trigger apoptosis. The prowess of cytotoxic lymphocytes to efficiently eradicate target cells has been widely harnessed in immunotherapies against haematological cancers. Despite efforts to achieve a similar outcome against solid tumours, the immunosuppressive and acidic tumour microenvironment poses a persistent obstacle. Using different types of effector cells, including therapeutically relevant anti-CD19 CAR T cells, we demonstrate that the acidic pH typically found in solid tumours hinders the efficacy of immune therapies by impeding perforin pore formation within the immunological synapse. A nanometre-scale study of purified recombinant perforin undergoing oligomerization reveals that pore formation is inhibited specifically by preventing the formation of a transmembrane β-barrel. The absence of perforin pore formation directly prevents target cell death. This finding uncovers a novel layer of immune effector inhibition that must be considered in the development of effective immunotherapies for solid tumours.

Effectiveness of mRNA COVID-19 vaccines and hybrid immunity in preventing SARS-CoV-2 infection and symptomatic COVID-19 among adults in the United States.

Understanding protection against SARS-CoV-2 infection by vaccine and hybrid immunity is important for informing public health strategies as new variants emerge. We analyzed data from three cohort studies spanning September 1, 2022-July 31, 2023, to estimate COVID-19 vaccine effectiveness (VE) against SARS-CoV-2 infection and symptomatic COVID-19 among adults with and without prior infection in the United States. Participants collected weekly nasal swabs, irrespective of symptoms, annual blood draws, and completed periodic surveys, which included vaccination status and prior infection history. Swabs were tested molecularly for SARS-CoV-2. VE was estimated using Cox proportional hazards models for the hazard ratios of infections, adjusting for covariates. VE was calculated considering prior infection and recency of vaccination. Among 3,344 adults, adjusted VE of bivalent vaccine against infection was 37.2% (95% CI: 12.3-55.7%) within 7-59 days of vaccination and 21.1% (95% CI: -0.5-37.1%) within 60-179 days of vaccination compared to participants who were unvaccinated/received an original monovalent vaccine dose ≥180 days prior. Overall, adjusted VE of bivalent vaccine against infection, in conjunction with prior infection, was 62.2% (95% CI: 46.0-74.5%) within 7-179 days of vaccination and 39.4% (95% CI: 12.5-61.6%) ≥180 days compared to naïve participants who were unvaccinated/received a monovalent vaccine dose ≥180 days prior. Adults with both prior infection and recent vaccination had high protection against infection and symptomatic illness. Recent vaccination alone provided moderate protection.

Immunotherapy on ICU: a narrative review.

Patients with cancer account for 15% of all admissions to critical care and so an understanding of the pathophysiology and anticipated complications of specialist treatment is essential for the intensive care clinician. The development of chimeric antigen receptor T-cell therapy for haematological malignancies and immune checkpoint inhibitors for solid organ tumours has led to significant improvements in the prognosis of those patients whose tumours respond. This review is intended to provide the non-specialist with an understanding of the current concepts in pathophysiology, diagnosis and management of complications due to chimeric antigen receptor T-cell therapy and immune checkpoint inhibitors for malignant disease. We performed searches of electronic databases to identify relevant peer-reviewed publications in the literature. Basic science; clinical trials; cohort studies; systematic reviews; meta-analyses; and guidelines were eligible for inclusion. Abstracts were screened to identify publications relevant to immune effector cell toxicities of chimeric antigen receptor T-cell therapy and immune-related adverse events of immune checkpoint inhibitors. While the pathophysiology for toxicities due to chimeric antigen receptor T-cells and immune checkpoint inhibitors remains incompletely understood, targeted drug therapies have been successfully implemented for toxicities such as cytokine release syndrome. Corticosteroids remain an important component of pharmacological management. The diagnosis of toxicities remains largely clinical, and a high index of suspicion should remain for infective complications. Management of toxicities should be undertaken in conjunction with the patient's primary oncologist. Despite significant advances in the development of targeted immunotherapy, the mechanism of action for the resultant toxicities remains poorly understood and limits the development of predictive models, diagnostic biomarkers and highly effective treatment options. Further research is needed to identify treatment regimens which minimise the use of corticosteroids in chimeric antigen receptor T-cell and immune checkpoint inhibitor-associated toxicities.

The Role of Electroencephalography Following CAR-T Cell Therapy in Clinical Practice.

Objectives:Neurotoxicity, encephalopathy, and seizures can occur following chimeric antigen receptor (CAR)-T cell therapy. Our aim was to assess what value electroencephalography (EEG) offers for people undergoing CAR-T treatment in clinical practice, including possible diagnostic, management, and prognostic roles. Methods: All patients developing CAR-T related neurotoxicity referred for EEG were eligible for inclusion. Reasons for EEG referral and qualitative EEG findings were analysed and reported. The relationship between objective quantitative EEG (QEEG) encephalopathy grade and clinical neurotoxicity (immune effector cell-associated neurotoxicity syndrome; ICANS) grade was determined. The prognostic ability of QEEG grade was assessed for survival and functional status. Results: Twenty-eight patients with 53 EEG recordings were included. Common reasons given on EEG referrals were possible seizure diagnosis (n = 38), reduced consciousness (n = 8), and superimposed cerebral infection (n = 4). Four focal seizures were detected on three (3/53; 5.7%) EEGs. There was a moderately positive correlation between QEEG grade and ICANS grade (r = + 0.41, p = .030). QEEG grade could not predict survival at 3 months (Area Under Curve; AUC = 0.673) or 6 months (AUC = 0.578), nor could it predict functional status at 1 month (r = + 0.40; p = .080), 3 months (r = + 0.19; p = .439), or time to return to baseline (r = + 0.32; p = .156). Conclusions: EEG was useful in seizure diagnosis. QEEG has a possible role as a specific biomarker of encephalopathy/neurotoxicity. EEG generated no tangible changes in patient management. QEEG was unable to prognosticate survival or functional status.

Evaluating the Immunoprotective and Diagnostic Potential of Schistosoma mansoni Epitopes from Sm050890 and Sm141290 Proteins Identified Through Reverse Vaccinology.

Schistosomiasis remains a parasitic disease affecting millions of people worldwide, requiring interventions like vaccination. In previous work, our group used reverse vaccinology to identify two epitopes from the Schistosoma mansoni proteins, Sm050890 (44-58) and Sm141290 (225-239). This study evaluated the immune response profile and protection induced by peptides, as a mixture of immunogens, in murine vaccination trials. Additionally, the diagnostic potential of these peptides was assessed on immunoassays. Mice were immunized with a formulation containing the mixture of the peptides, subsequently infected, and perfused for worm burden recovery and quantification. Liver and blood samples from animals were used to evaluate the effect of immunization on the formation of granulomas and specific anti-peptide antibodies (IgG). Additionally, cytokine measurement was performed in splenocyte cultures from immunized mice, and peripheral blood serum from individuals infected with S. mansoni was used to assess the recognition of the peptides by IgG antibodies. The vaccine stimulated an increase in the production of IgG and IgG2c antibodies, associated with a significant reduction of 44 - 29% in worm burden. Although the vaccine did not reduce liver pathology, it enhanced the production of IFN-γ while decreasing IL-10 production by splenocytes. Furthermore, the peptides Sm050890 (44-58) and Sm141290 (225-239) were not recognized by IgG antibodies in the serum from infected individuals. Overall, our data suggest that the peptides Sm050890 (44-58) and Sm141290 (225-239) are promising vaccine candidates against schistosomiasis and can be used to compose a multiepitope/chimeric vaccine in future studies.

How macrophage heterogeneity affects tuberculosis disease and therapy.

Macrophages are the primary host cell type for infection by Mycobacterium tuberculosis in vivo. Macrophages are also key immune effector cells that mediate the control of bacterial growth. However, the specific macrophage phenotypes that are required for optimal immune control of M.tuberculosis infection in vivo remain poorly defined. There are two distinct macrophage lineages in the lung, comprising embryonically derived, tissue-resident alveolar macrophages and recruited, blood monocyte-derived interstitial macrophages. Recent studies have shown that these lineages respond divergently to similar immune environments within the tuberculosis granuloma. Here, we discuss how the differing responses of macrophage lineages might affect the control or progression of tuberculosis disease. We suggest that the ability to reprogramme macrophage responses appropriately, through immunological or chemotherapeutic routes, could help to optimize vaccines and drug regimens for tuberculosis.