Review
Immunology
Fangzheng Guo, Jing Wei, Yamin Song, Baiqing Li, Zhongqing Qian, Xiaojing Wang, Hongtao Wang, Tao Xu
Summary: Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis. While the BCG vaccine has been widely administered, its protective rate in preventing tuberculosis is not high in some regions, especially in adults. Therefore, research on the Mtb mechanism and development of new vaccines are crucial strategies. Recent studies have highlighted the role of PE and PPE proteins in the pathogenesis and chronic infection observed in TB, leading to the development of vaccines based on Mtb antigens.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Yuchen Wang, Yuting Tang, Chen Lin, Junli Zhang, Juntao Mai, Jun Jiang, Xiaoxiao Gao, Yao Li, Guoping Zhao, Lu Zhang, Jun Liu
Summary: The ESX-4 system in Mycobacterium marinum does not secrete its cognate substrates, but the deletion of eccC4, an essential component of ESX-4, resulted in elevated secretion of protein substrates of ESX-1 and ESX-5, leading to enhanced phagocytosis by macrophages.
Article
Immunology
Christopher D'Souza, Uday Kishore, Anthony G. Tsolaki
Summary: Mycobacterium tuberculosis has been infecting a third of the world's population and the PE-PPE protein family has been identified as a key factor in its pathogenesis. Despite extensive research, many important questions about these proteins remain unanswered.
Article
Microbiology
Paula Josefina Gomez-Gonzalez, Anna D. Grabowska, Leopold D. Tientcheu, Anthony G. Tsolaki, Martin L. Hibberd, Susana Campino, Jody E. Phelan, Taane G. Clark
Summary: This study investigated the genetic diversity of the mat genes in Mycobacterium tuberculosis and found that these genes are highly conserved among different strains, although some variations were observed. Understanding the diversity and conservation of the mat genes can provide insights into the genetic pathogenesis of tuberculosis and contribute to the development of new strategies for tuberculosis control.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Microbiology
Merel P. M. Damen, Aniek S. Meijers, Esther M. Keizer, Sander R. Piersma, Connie R. Jimenez, Coenraad P. Kuijl, Wilbert Bitter, Edith N. G. Houben
Summary: Pathogenic mycobacteria utilize the ESX-1 secretion system to mediate intracellular survival, but determining the responsible ESX-1 substrate is challenging due to complex secretion dependencies. This study reveals the critical role of the ESX-1 substrate PPE68 in mediating the secretion of ESX-1 substrates in Mycobacterium marinum, providing insights into the functional understanding of T7SSs and the virulence of Mycobacterium tuberculosis.
Article
Biochemistry & Molecular Biology
Deepa Paliwal, Michelle Thom, Areej Hussein, Divyashree Ravishankar, Alex Wilkes, Bryan Charleston, Ian M. Jones
Summary: Bovine tuberculosis caused by Mycobacterium bovis is a significant global pathogen that affects livestock and can also infect humans. This study focuses on developing a vaccine using reverse vaccinology approach. By cloning and expressing 123 ORFs from the M. bovis genome, the researchers provided feasibility data for this approach. The majority of the cloned proteins showed soluble expression, making them suitable for potential test immunizations in the development of an effective bovine tuberculosis vaccine.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Parasitology
Medha, Sadhna Sharma, Monika Sharma
Summary: The PE/PPE proteins encoded by 7% of the Mtb genome are key components of the pathogen's virulence reservoir. While speculation abounds about their role at the host-pathogen interface and in disease pathogenesis, their exact function remains a mystery, highlighting the need for further research targeting these proteins. These proteins are thought to play a versatile role as host immune sensors and crucial factors in shaping the outcome of Tuberculosis infection, with the potential to pave the way for new vaccines and therapeutics.
Review
Immunology
Cheldon Ann Alcantara, Ira Glassman, Kevin H. Nguyen, Arpitha Parthasarathy, Vishwanath Venketaraman
Summary: Mycobacterium tuberculosis (M. tb) remains a major cause of death in developing countries. The BCG vaccine is widely used in developing countries but its efficacy is still uncertain. Neutrophils play a crucial role in the immune response against M. tb, promoting clearance of the bacteria and regulating the inflammatory response. This review highlights the role of neutrophils during M. tb infection and emphasizes the need for more research on effective vaccination.
Article
Biochemistry & Molecular Biology
Pradeep Kumar Anand, Gagandeep Kaur, Varinder Saini, Jasbinder Kaur, Jagdeep Kaur
Summary: The multigene PE/PPE family is found exclusively in mycobacterium species. Rv3539, identified as PPE63, contains a conserved PPE domain at the N-terminal and a PE-PPE domain at the C-terminal. The study shows that Rv3539 has esterase activity, with the PE-PPE domain demonstrating higher enzyme activity. Additionally, the PPE domain is important for the thermostability and structural integrity of Rv3539.
Article
Immunology
Mariana Herrera, Yoav Keynan, Lucelly Lopez, Diana Marin, Lazaro Velez, Paul J. McLaren, Zulma Vanessa Rueda
Summary: We studied the immune changes in newly acquired tuberculosis infection in a population deprived of liberty in Colombian prisons. We found differences in immune levels between individuals with new tuberculosis infection and those incarcerated for short and long periods of time. Certain cytokines/chemokines were associated with new tuberculosis infection and tuberculosis disease.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Stephanie Fischinger, Deniz Cizmeci, Sally Shin, Leela Davies, Patricia S. Grace, Aida Sivro, Nonhlanhla Yende-Zuma, Hendrik Streeck, Sarah M. Fortune, Douglas A. Lauffenburger, Kogieleum Naidoo, Galit Alter
Summary: South Africa has the highest prevalence of HIV and tuberculosis co-infection globally, with HIV infected individuals having a greater likelihood of developing recurrent TB. This study investigated the humoral response in HIV co-infected individuals with and without recurrent TB, finding differences in antibody profiles, particularly decreased Mtb-antigen specific IgG3 titers in individuals with recurrent TB. These findings suggest a potential role for Mtb-specific IgG3 responses as biomarkers or mediators of protective immunity against Mtb recurrence.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemical Research Methods
Paula J. Gomez-Gonzalez, Susana Campino, Jody E. Phelan, Taane G. Clark
Summary: This study compared the genome sequencing of clinical isolates of Mycobacterium tuberculosis using Oxford Nanopore Technologies (ONT) sequencing and Illumina HiSeq sequencing. The analysis showed that ONT sequencing is robust for detecting single nucleotide polymorphisms and provides improved coverage in repetitive regions. It also demonstrated high concordance in variants associated with drug resistance. ONT sequencing is a promising tool for tuberculosis genomic investigations and can inform clinical and surveillance decision-making to reduce the disease burden.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Immunology
Shuping Li, Xiaohua Wang, Yuming Zhao, Juan Yang, Tianjiao Cui, Zhizhuang Joe Zhao, Yun Chen, Zhihua Zheng
Summary: The PTPN22-C1858T polymorphism is not significantly associated with higher susceptibility to M. tuberculosis infection in Caucasians and Asians, but is relevant to increased susceptibility to M. leprae infection. Further well-designed studies with sufficient populations are required to verify these conclusions.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Medha, Priyanka, Sadhna Sharma, Monika Sharma
Summary: In this study, we targeted 34 late-stage PE/PPE proteins of Mtb to predict and identify promiscuous and cross-reactive epitopes, resulting in the discovery of 149 epitopes of which 42 were antigenic. The top 10 CD4(+) T cell specific, antigenic peptide epitopes were characterized as non-allergenic and pro-inflammatory, with strong affinity for MHC class I and wide population coverage globally. Additionally, molecular docking studies and in silico cloning of a recombinant vaccine construct incorporating selected epitopes showed potential for an effective TB vaccine.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Review
Immunology
Nan Wang, Yongliang Yao, Yingfen Qian, Dewen Qiu, Hui Cao, Huayuan Xiang, Jianjun Wang
Summary: Exosomes are double-membrane vesicles containing various lipids, proteins, mRNAs, and non-coding RNAs, and are involved in multiple physiological processes such as intercellular communication and immunomodulation. Studies have found that the components of exosomes released from host cells are altered following Mycobacterium tuberculosis infection. The contents of exosomes provide excellent biomarkers for the diagnosis, efficacy evaluation, and prognosis of tuberculosis.
FRONTIERS IN IMMUNOLOGY
(2023)
Letter
Oncology
Silvia Bellesi, Michela Sali, Elena Maiolo, Maria del Carmen Pereyra Boza, Eleonora Alma, Ivana Palucci, Federica Fatone, Flavio De Maio, Marcello Viscovo, Francesco D'Alo, Valerio De Stefano, Stefan Hohaus, Maurizio Sanguinetti
LEUKEMIA & LYMPHOMA
(2022)
Article
Multidisciplinary Sciences
Maria Tredicine, Chiara Camponeschi, Davide Pirolli, Matteo Lucchini, Mariagrazia Valentini, Maria Concetta Geloso, Massimiliano Mirabella, Marco Fidaleo, Benedetta Righino, Camilla Moliterni, Ezio Giorda, Mario Rende, Maria Cristina De Rosa, Maria Foti, Gabriela Constantin, Francesco Ria, Gabriele Di Sante
Summary: The modulation of leukocyte trafficking, specifically the effect of TLR2 ligands on the reshuffling of CD44 isoforms repertoire in T helper cells, plays a crucial role in the pathogenesis of autoimmune disorders. The strain background and TLR2 haplotype also affect the Wnt/β-catenin signaling pathway and expression of splicing factors. This study suggests that TLRs regulation of CD44 isoform repertoire may control the distribution of lesions in the central nervous system.
Article
Microbiology
Francesca Boldrin, Laura Cioetto Mazzabo, Marie-Antoinette Laneelle, Laura Rindi, Greta Segafreddo, Anne Lemassu, Gilles Etienne, Marta Conflitti, Mamadou Daffe, Alfredo Garzino Demo, Riccardo Manganelli, Hedia Marrakchi, Roberta Provvedi
Summary: In this study, we characterized a protein encoded by the Mtb genome, Rv1619, and found that it is a potential member of the aaPG synthase family. Unlike previous studies, we predicted that the MprF-like domain of Rv1619 is located in the extracytoplasmic region.
Article
Pediatrics
Gabriele Di Sante, Danilo Buonsenso, Cristina De Rose, Maria Tredicine, Ivana Palucci, Flavio De Maio, Chiara Camponeschi, Nicola Bonadia, Daniele Biasucci, Davide Pata, Antonio Chiaretti, Piero Valentini, Francesco Ria, Maurizio Sanguinetti, Michela Sali
Summary: While COVID-19 has a massive clinical impact on adults, children mostly experience mild or even asymptomatic infections. This study found differences in cytokine levels and T and B cell subpopulations between infected children and adults, suggesting distinct immunopathology in pediatric infection. These findings could potentially inform vaccination strategies for children.
Article
Medicine, General & Internal
Danilo Buonsenso, Piero Valentini, Cristina De Rose, Maria Tredicine, Maria del Carmen Pereyra Boza, Chiara Camponeschi, Rosa Morello, Giuseppe Zampino, Anna E. S. Brooks, Mario Rende, Francesco Ria, Maurizio Sanguinetti, Giovanni Delogu, Michela Sali, Gabriele Di Sante
Summary: This study investigated the cellular immunological responses of children with COVID-19, including those with acute infection, recovered individuals, and those with persistent symptoms. The study found that children with long-term COVID may have compromised adaptive immune responses and imbalances in T and B cell subsets, which could contribute to the persistence of symptoms.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Neurosciences
Matteo Lucchini, Valeria De Arcangelis, Geny Piro, Viviana Nociti, Assunta Bianco, Chiara De Fino, Gabriele Di Sante, Francesco Ria, Paolo Calabresi, Massimiliano Mirabella
Summary: This study assessed the concentration of several biomarkers in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients and investigated their diagnostic and prognostic significance. The results showed that higher CSF levels of CHI3L1 and CXCL13 were associated with a higher risk of relapse, MRI activity, and overall disease activity in MS patients. These findings suggest that CSF CHI3L1 and CXCL13 levels can serve as good prognostic biomarkers in MS patients and aid in treatment decisions. The study also found differences in CSF BAFF and APRIL levels between different phases of MS, indicating the modulation of B-cells pathways vary in different disease stages.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Engineering, Biomedical
Maria Tredicine, Francesco Ria, Noemi Poerio, Matteo Lucchini, Assunta Bianco, Federica De Santis, Mariagrazia Valentini, Valeria De Arcangelis, Mario Rende, Anna Maria Stabile, Alessandra Pistilli, Chiara Camponeschi, Viviana Nociti, Massimiliano Mirabella, Maurizio Fraziano, Gabriele Di Sante
Summary: The current available treatments of Multiple Sclerosis (MS) have limited efficacy in slowing the progression of the disease and can lead to severe side effects. This study evaluated the immunomodulatory potential of a new class of nanoparticles called liposomes in vitro. The results showed that liposomes composed of phosphatidylserine were able to inhibit inflammatory cytokine secretion and expand regulatory T cells. These findings suggest that liposomes could be used as therapeutic tools to dampen pro-inflammatory immune responses and promote regulatory immune responses in MS.
Article
Biochemistry & Molecular Biology
Ivana Palucci, Alessandro Salustri, Flavio De Maio, Maria del Carmen Pereyra Boza, Francesco Paglione, Michela Sali, Luca Occhigrossi, Manuela D'Eletto, Federica Rossin, Delia Goletti, Maurizio Sanguinetti, Mauro Piacentini, Giovanni Delogu
Summary: This study aimed to test the potential activity of cysteamine and cystamine against Mycobacterium abscessus. The results showed that these drugs restricted the growth of M. abscessus in human macrophages and had enhanced activity when combined with amikacin. The treatment with these drugs was more effective against MAB-S infection and reduced the inflammatory response triggered by MAB-R infection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Materials Science, Textiles
Flavio De Maio, Giulia Santarelli, Valentina Palmieri, Giordano Perini, Alessandro Salustri, Ivana Palucci, Giovanni Delli Carpini, Alberto Augello, Maurizio Sanguinetti, Marco De Spirito, Michela Sali, Giovanni Delogu, Massimiliano Papi
Summary: Respiratory tract infections are the leading cause of death from infectious diseases globally, with COVID-19 adding to the burden of existing respiratory tract infections like tuberculosis. Graphene and curcumin can be used to create fabric coatings on cotton and polyester, providing personal protective equipment that is resistant to infectious agents.
JOURNAL OF NATURAL FIBERS
(2023)
Article
Multidisciplinary Sciences
Davide Pirolli, Benedetta Righino, Chiara Camponeschi, Francesco Ria, Gabriele Di Sante, Maria Cristina De Rosa
Summary: After over two years of living with Covid-19 and the rapid mutation of its genome, there is still a need to find proper treatments for the novel coronavirus. A drug repositioning study was conducted using in silico tools to target the Delta Spike protein/ACE2 interface. Virtual screening of approved drugs identified four compounds that showed stable binding modes on Delta Spike RBD and were evaluated for effectiveness against Omicron. Among them, fexofenadine, an antihistamine drug, demonstrated low binding energy, stable complex, and interesting interactions with Delta Spike RBD. The study highlights the potential of computational methodology for rapid screening of variant-specific drugs and provides a tool for investigating properties and mechanisms of selected drugs.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Maria Elisabetta Clementi, Beatrice Sampaolese, Gabriele Di Sante, Francesco Ria, Rosa Di Liddo, Vincenzo Romano Spica, Fabrizio Michetti
Summary: The study demonstrated that the expression of S100B in astrocytoma cells plays a crucial role in the activation of reactive astrocytic processes, including cytotoxicity, ROS and NOS activation. Silencing S100B in astrocytoma cells effectively protected the cells from amyloid beta-peptide-induced damage, reducing cell death, oxygen radical generation and nitric oxide synthase activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Alessandro Salustri, Flavio De Maio, Valentina Palmieri, Giulia Santarelli, Ivana Palucci, Delia Mercedes Bianco, Federica Marchionni, Silvia Bellesi, Gabriele Ciasca, Giordano Perini, Maurizio Sanguinetti, Michela Sali, Massimiliano Papi, Marco De Spirito, Giovanni Delogu
Summary: Graphene Oxide has been proposed as a potential adjuvant to improve anti-TB treatment by trapping mycobacteria and limiting their entry into macrophages. However, our findings show that graphene oxide is not effective in clearing Mycobacterium tuberculosis in human immune cells, possibly due to its toxic effects on monocytes and CD4+ lymphocytes.
Article
Biochemistry & Molecular Biology
Chiara Camponeschi, Benedetta Righino, Davide Pirolli, Alessandro Semeraro, Francesco Ria, Maria Cristina De Rosa
Summary: CD44 is a cell surface glycoprotein transmembrane receptor that interacts with other cells and the extracellular matrix. It is widely expressed and regulates important signaling pathways, playing a crucial role in physiological and pathological processes. Understanding the structure of CD44 is essential for developing treatments for its dysregulation in diseases. Using deep-learning-based tools, researchers predicted the structure of the full-length CD44 receptor and identified its key functional regions.
Article
Biochemistry & Molecular Biology
Vincenzo Romano Spica, Federica Valeriani, Massimiliano Orsini, Maria Elisabetta Clementi, Luisa Seguella, Gianluca Gianfranceschi, Rosa Di Liddo, Gabriele Di Sante, Francesca Ubaldi, Francesco Ria, Giuseppe Esposito, Fabrizio Michetti
Summary: This in vivo study investigates the relationship between microbiota biodiversity and the levels of S100B protein. The results show a significant positive correlation between S100B levels and Shannon values, which can be influenced by the modulation of S100B activity. Three distinct groups were identified based on the distribution of S100B concentration, with significant differences in microbial profiles. The administration of S100B orally resulted in modified microbial composition. These findings suggest the potential role of S100B in regulating the intestinal microbiota.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Marco Perulli, Gianpaolo Cicala, Ida Turrini, Elisa Musto, Michela Quintiliani, Maria Luigia Gambardella, Silvia Maria Pulitano, Sarah Bompard, Susanna Staccioli, Laura Carmillo, Gabriele Di Sante, Francesco Ria, Chiara Veredice, Ilaria Contaldo, Domenica Battaglia
Summary: Febrile infection-related epilepsy syndrome (FIRES) is a challenging condition with unfavorable outcome in most cases. Preliminary evidence suggests that elevated levels of certain interleukins may be related to a functional deficiency in anti-inflammatory pathways. Therefore, targeting innate immunity in treatment strategies may be effective. This case study describes a successful treatment approach using anakinra and a ketogenic diet for a patient with super-refractory status epilepticus (SE). High levels of IL-1RA in the patient's serum supported the escalation of therapy. After more than one year follow-up, the patient is seizure-free with moderate intellectual disability but good language skills. This case suggests that serum IL-1RA levels could be helpful in guiding treatment escalation and that anakinra and ketogenic diet show promise as immunomodulatory strategies.
EPILEPSY & BEHAVIOR REPORTS
(2022)
