المؤلفون: Abhishek Mishra, Arshad Khan, Vipul Kumar Singh, Emily Glyde, Sankaralingam Saikolappan, Omar Garnica, Kishore Das, Raja Veerapandian, Subramanian Dhandayuthapani, Chinnaswamy Jagannath

المصدر: Frontiers in Immunology, Vol 15 (2024)

مصطلحات موضوعية: tuberculosis, vaccine, Mtb-derived, live vaccine, immunogenic, macrophages, Immunologic diseases. Allergy, RC581-607

الوصف: Tuberculosis (TB) remains a significant global health challenge, with approximately 1.5 million deaths per year. The Bacillus Calmette-Guérin (BCG) vaccine against TB is used in infants but shows variable protection. Here, we introduce a novel approach using a double gene knockout mutant (DKO) from wild-type Mycobacterium tuberculosis (Mtb) targeting fbpA and sapM genes. DKO exhibited enhanced anti-TB gene expression in mouse antigen-presenting cells, activating autophagy and inflammasomes. This heightened immune response improved ex vivo antigen presentation to T cells. Subcutaneous vaccination with DKO led to increased protection against TB in wild-type C57Bl/6 mice, surpassing the protection observed in caspase 1/11-deficient C57Bl/6 mice and highlighting the critical role of inflammasomes in TB protection. The DKO vaccine also generated stronger and longer-lasting protection than the BCG vaccine in C57Bl/6 mice, expanding both CD62L-CCR7-CD44+/-CD127+ effector T cells and CD62L+CCR7+/-CD44+CD127+ central memory T cells. These immune responses correlated with a substantial ≥ 1.7-log10 reduction in Mtb lung burden. The DKO vaccine represents a promising new approach for TB immunization that mediates protection through autophagy and inflammasome pathways.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2024.1321657/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/50fe6729025b4050bf607384e5c03d58Test

المؤلفون: Enrique I. Ramos, Raja Veerapandian, Kishore Das, Jessica A. Chacon, Shrikanth S. Gadad, Subramanian Dhandayuthapani

المصدر: Non-coding RNA Research, Vol 8, Iss 3, Pp 282-293 (2023)

مصطلحات موضوعية: Mycoplasma, Epithelial cells, Gene expression analyses, Long non-coding RNAs, Genetics, QH426-470

الوصف: Non-coding RNAs (ncRNAs), specifically long ncRNAs (lncRNAs), regulate cellular processes by affecting gene expression at the transcriptional, post-transcriptional, and epigenetic levels. Emerging evidence indicates that pathogenic microbes dysregulate the expression of host lncRNAs to suppress cellular defense mechanisms and promote survival. To understand whether the pathogenic human mycoplasmas dysregulate host lncRNAs, we infected HeLa cells with Mycoplasma genitalium (Mg) and Mycoplasma penumoniae (Mp) and assessed the expression of lncRNAs by directional RNA-seq analysis. HeLa cells infected with these species showed up-and-down regulation of lncRNAs expression, indicating that both species can modulate host lncRNAs. However, the number of upregulated (200 for Mg and 112 for Mp) and downregulated lncRNAs (30 for Mg and 62 for Mp) differ widely between these two species. GREAT analysis of the noncoding regions associated with differentially expressed lncRNAs showed that Mg and Mp regulate a discrete set of lncRNA plausibly related to transcription, metabolism, and inflammation. Further, signaling network analysis of the differentially regulated lncRNAs exhibited diverse pathways such as neurodegeneration, NOD-like receptor signaling, MAPK signaling, p53 signaling, and PI3K signaling, suggesting that both species primarily target signaling mechanisms. Overall, the study's results suggest that Mg and Mp modulate lncRNAs to promote their survival within the host but in distinct manners.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2468054023000124Test; https://doaj.org/toc/2468-0540Test

الوصول الحر: https://doaj.org/article/da66cb84b2e94748bf4cfad9d6d75d2bTest

المؤلفون: Raja Veerapandian, Shrikanth S. Gadad, Chinnaswamy Jagannath, Subramanian Dhandayuthapani

المصدر: Vaccines, Vol 12, Iss 5, p 530 (2024)

مصطلحات موضوعية: tuberculosis, live attenuated vaccines (LAVs), gene knockout, Mycobacterium tuberculosis, BCG, secretory antigens, Medicine

الوصف: Tuberculosis (TB), a chronic infectious disease affecting humans, causes over 1.3 million deaths per year throughout the world. The current preventive vaccine BCG provides protection against childhood TB, but it fails to protect against pulmonary TB. Multiple candidates have been evaluated to either replace or boost the efficacy of the BCG vaccine, including subunit protein, DNA, virus vector-based vaccines, etc., most of which provide only short-term immunity. Several live attenuated vaccines derived from Mycobacterium tuberculosis (Mtb) and BCG have also been developed to induce long-term immunity. Since Mtb mediates its virulence through multiple secreted proteins, these proteins have been targeted to produce attenuated but immunogenic vaccines. In this review, we discuss the characteristics and prospects of live attenuated vaccines generated by targeting the disruption of the genes encoding secretory mycobacterial proteins.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2076-393X/12/5/530Test; https://doaj.org/toc/2076-393XTest

الوصول الحر: https://doaj.org/article/bafa08b414094cab88bc47a4892dcf2dTest

المؤلفون: Enrique I. Ramos, Kishore Das, Alana L. Harrison, Anissa Garcia, Shrikanth S. Gadad, Subramanian Dhandayuthapani

المصدر: Frontiers in Immunology, Vol 12 (2021)

مصطلحات موضوعية: mycoplasma, epithelial cells, interactions, RNA-seq, gene expression, protein-coding, Immunologic diseases. Allergy, RC581-607

الوصف: Mycoplasma genitalium and M. pneumoniae are two significant mycoplasmas that infect the urogenital and respiratory tracts of humans. Despite distinct tissue tropisms, they both have similar pathogenic mechanisms and infect/invade epithelial cells in the respective regions and persist within these cells. However, the pathogenic mechanisms of these species in terms of bacterium-host interactions are poorly understood. To gain insights on this, we infected HeLa cells independently with M. genitalium and M. pneumoniae and assessed gene expression by whole transcriptome sequencing (RNA-seq) approach. The results revealed that HeLa cells respond to M. genitalium and M. pneumoniae differently by regulating various protein-coding genes. Though there is a significant overlap between the genes regulated by these species, many of the differentially expressed genes were specific to each species. KEGG pathway and signaling network analyses revealed that the genes specific to M. genitalium are more related to cellular processes. In contrast, the genes specific to M. pneumoniae infection are correlated with immune response and inflammation, possibly suggesting that M. pneumoniae has some inherent ability to modulate host immune pathways.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2021.738431/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/5a4f1224f6bd4a57820f92380686c503Test

المؤلفون: Yae Kye, Lokesh Nagineni, Shrikanth Gadad, Fabiola Ramirez, Hannah Riva, Lorena Fernandez, Michelle Samaniego, Nathan Holland, Rose Yeh, Kei Takigawa, Subramanian Dhandayuthapani, Jessica Chacon

المصدر: Cancers, Vol 14, Iss 17, p 4255 (2022)

مصطلحات موضوعية: mutated antigen, neoantigen, immunotherapy, tumor-associated antigens, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: The era of personalized cancer therapy is here. Advances in the field of immunotherapy have paved the way for the development of individualized neoantigen-based therapies that can translate into favorable treatment outcomes and fewer side effects for patients. Addressing challenges related to the identification, access, and clinical application of neoantigens is critical to accelerating the development of individualized immunotherapy for cancer patients.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2072-6694/14/17/4255Test; https://doaj.org/toc/2072-6694Test

الوصول الحر: https://doaj.org/article/51cd9504a1bf4780af3585671992a2c2Test

المؤلفون: Ilene Le, Subramanian Dhandayuthapani, Jessica Chacon, Anna M. Eiring, Shrikanth S. Gadad

المصدر: Vaccines, Vol 10, Iss 5, p 816 (2022)

مصطلحات موضوعية: cancer, cancer vaccines, antigens, immunotherapy, Medicine

الوصف: Prophylactic vaccination against infectious diseases is one of the most successful public health measures of our lifetime. More recently, therapeutic vaccination against established diseases such as cancer has proven to be more challenging. In the host, cancer cells evade immunologic regulation by multiple means, including altering the antigens expressed on their cell surface or recruiting inflammatory cells that repress immune surveillance. Nevertheless, recent clinical data suggest that two classes of antigens show efficacy for the development of anticancer vaccines: tumor-associated antigens and neoantigens. In addition, many different vaccines derived from antigens based on cellular, peptide/protein, and genomic components are in development to establish their efficacy in cancer therapy. Some vaccines have shown promising results, which may lead to favorable outcomes when combined with standard therapeutic approaches. This review provides an overview of the innate and adaptive immune systems, their interactions with cancer cells, and the development of various different vaccines for use in anticancer therapeutics.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2076-393X/10/5/816Test; https://doaj.org/toc/2076-393XTest

الوصول الحر: https://doaj.org/article/896de51360ce40c9a7484ca50fc2cb7dTest

المؤلفون: Omar A. Garnica, Kishore Das, Subramanian Dhandayuthapani

المصدر: Scientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)

مصطلحات موضوعية: Medicine, Science

الوصف: Abstract Organic hydroperoxide reductase regulator (OhrR) in bacteria is a sensor for organic hydroperoxide stress and a transcriptional regulator for the enzyme organic hydroperoxide reductase (Ohr). In this study we investigated, using a GFP reporter system, whether Mycobacterium smegmatis OhrR has the ability to sense and respond to intracellular organic hydroperoxide stress. It was observed that M. smegmatis strains bearing the pohr-gfpuv fusion construct were able to express GFP only in the absence of an intact ohrR gene, but not in its presence. However, GFP expression in the strain bearing pohr-gfpuv with an intact ohrR gene could be induced by organic hydroperoxides in vitro and in the intracellular environment upon ingestion of the bacteria by macrophages; indicating that OhrR responds not only to in vitro but also to intracellular organic hydroperoxide stress. Further, the intracellular expression of pohr driven GFP in this strain could be abolished by replacing the intact ohrR gene with a mutant ohrR gene modified for N-terminal Cysteine (Cys) residue, suggesting that OhrR senses intracellular organic hydroperoxides through Cys residue. This is the first report demonstrating the ability of OhrR to sense intracellular organic hydroperoxides.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-2322Test

الوصول الحر: https://doaj.org/article/9ed85bc954994bb2ab572db0149b2de2Test

المؤلفون: Kishore Das, Omar Garnica, Subramanian Dhandayuthapani

المصدر: Frontiers in Cellular and Infection Microbiology, Vol 6 (2016)

مصطلحات موضوعية: Francisella, Listeria, Macrophages, Mycobacterium, Salmonella, microRNA, Microbiology, QR1-502

الوصف: MicroRNAs (miRNAs) are short non-coding RNAs that regulate the expression of protein coding genes of viruses and eukaryotes at the post-transcriptional level. The eukaryotic genes regulated by miRNAs include those whose products are critical for biological processes such as cell proliferation, metabolic pathways, immune response, and development. It is now increasingly recognized that modulation of miRNAs associated with biological processes is one of the strategies adopted by bacterial pathogens to survive inside the host cells. In this review, we present an overview of the recent findings on alterations of miRNAs in the host cells by facultative intracellular bacterial pathogens. In addition, we discuss how the altered miRNAs help in the survival of these pathogens in the intracellular environment.

وصف الملف: electronic resource

العلاقة: http://journal.frontiersin.org/Journal/10.3389/fcimb.2016.00079/fullTest; https://doaj.org/toc/2235-2988Test

الوصول الحر: https://doaj.org/article/e3f5c83b15674a91b58833c11c9b971fTest

المؤلفون: Kishore Das, Georgina De la Garza, Shivani Maffi, Sankaralingam Saikolappan, Subramanian Dhandayuthapani

المصدر: PLoS ONE, Vol 7, Iss 4, p e36247 (2012)

مصطلحات موضوعية: Medicine, Science

الوصف: Mycoplasma genitalium is an important sexually transmitted pathogen that affects both men and women. In genital-mucosal tissues, it initiates colonization of epithelial cells by attaching itself to host cells via several identified bacterial ligands and host cell surface receptors. We have previously shown that a mutant form of M. genitalium lacking methionine sulfoxide reductase A (MsrA), an antioxidant enzyme which converts oxidized methionine (Met(O)) into methionine (Met), shows decreased viability in infected animals. To gain more insights into the mechanisms by which MsrA controls M. genitalium virulence, we compared the wild-type M. genitalium strain (G37) with an msrA mutant (MS5) strain for their ability to interact with target cervical epithelial cell lines (HeLa and C33A) and THP-1 monocytic cells. Infection of epithelial cell lines with both strains revealed that MS5 was less cytotoxic to HeLa and C33A cell lines than the G37 strain. Also, the MS5 strain was more susceptible to phagocytosis by THP-1 cells than wild type strain (G37). Further, MS5 was less able to induce aggregation and differentiation in THP-1 cells than the wild type strain, as determined by carboxyfluorescein diacetate succinimidyl ester (CFSE) labeling of the cells, followed by counting of cells attached to the culture dish using image analysis. Finally, MS5 was observed to induce less proinflammatory cytokine TNF-α by THP-1 cells than wild type G37 strain. These results indicate that MsrA affects the virulence properties of M. genitalium by modulating its interaction with host cells.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC3340341?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/5cbcca062f934aacb9f5e91b8879ccd1Test

المؤلفون: Sankaralingam Saikolappan, Jaymie Estrella, Smitha J Sasindran, Arshad Khan, Lisa Y Armitige, Chinnaswamy Jagannath, Subramanian Dhandayuthapani

المصدر: PLoS ONE, Vol 7, Iss 5, p e36198 (2012)

مصطلحات موضوعية: Medicine, Science

الوصف: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is the leading cause of death due to bacterial infections in mankind, and BCG, an attenuated strain of Mycobacterium bovis, is an approved vaccine. BCG sequesters in immature phagosomes of antigen presenting cells (APCs), which do not fuse with lysosomes, leading to decreased antigen processing and reduced Th1 responses. However, an Mtb derived ΔfbpA attenuated mutant underwent limited phagosome maturation, enhanced immunogenicity and was as effective as BCG in protecting mice against TB. To facilitate phagosome maturation of ΔfbpA, we disrupted an additional gene sapM, which encodes for an acid phosphatase. Compared to the wild type Mtb, the ΔfbpAΔsapM (double knock out; DKO) strain was attenuated for growth in mouse macrophages and PMA activated human THP1 macrophages. Attenuation correlated with increased oxidants in macrophages in response to DKO infection and enhanced labeling of lysosomal markers (CD63 and rab7) on DKO phagosomes. An in vitro Antigen 85B peptide presentation assay was used to determine antigen presentation to T cells by APCs infected with DKO or other mycobacterial strains. This revealed that DKO infected APCs showed the strongest ability to present Ag85B to T cells (>2500 pgs/mL in 4 hrs) as compared to APCs infected with wild type Mtb or ΔfbpA or ΔsapM strain (

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC3344844?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/672ddd42e9df404581348357b7631dc4Test