scholarly journals Mycobacterium tuberculosis adhesins: potential biomarkers as anti-tuberculosis therapeutic and diagnostic targets

Microbiology ◽  
2014 ◽  
Vol 160 (9) ◽  
pp. 1821-1831 ◽  
Author(s):  
Viveshree S. Govender ◽  
Saiyur Ramsugit ◽  
Manormoney Pillay
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Control Strategies ◽  
Host Cells ◽  
Tuberculosis Control ◽  
Surface Molecules ◽  
Host Pathogen Interaction ◽  
Bacterial Aggregation ◽  
Insight Into

Adhesion to host cells is a precursor to host colonization and evasion of the host immune response. Conversely, it triggers the induction of the immune response, a process vital to the host’s defence against infection. Adhesins are microbial cell surface molecules or structures that mediate the attachment of the microbe to host cells and thus the host–pathogen interaction. They also play a crucial role in bacterial aggregation and biofilm formation. In this review, we discuss the role of adhesins in the pathogenesis of the aetiological agent of tuberculosis, Mycobacterium tuberculosis. We also provide insight into the structure and characteristics of some of the characterized and putative M. tuberculosis adhesins. Finally, we examine the potential of adhesins as targets for the development of tuberculosis control strategies.

scholarly journals Bacterial Cyclic Dinucleotides and the cGAS–cGAMP–STING Pathway: A Role in Periodontitis?

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 675
Author(s):  
Samira Elmanfi ◽  
Mustafa Yilmaz ◽  
Wilson W. S. Ong ◽  
Kofi S. Yeboah ◽  
Herman O. Sintim ◽  
...  
Keyword(s):  
Immune Response ◽  
Periodontal Disease ◽  
Innate Immune ◽  
Host Cells ◽  
Type I Interferons ◽  
Type I ◽  
Vaccine Adjuvants ◽  
Cyclic Dinucleotides ◽  
Sting Pathway

Host cells can recognize cytosolic double-stranded DNAs and endogenous second messengers as cyclic dinucleotides—including c-di-GMP, c-di-AMP, and cGAMP—of invading microbes via the critical and essential innate immune signaling adaptor molecule known as STING. This recognition activates the innate immune system and leads to the production of Type I interferons and proinflammatory cytokines. In this review, we (1) focus on the possible role of bacterial cyclic dinucleotides and the STING/TBK1/IRF3 pathway in the pathogenesis of periodontal disease and the regulation of periodontal immune response, and (2) review and discuss activators and inhibitors of the STING pathway as immune response regulators and their potential utility in the treatment of periodontitis. PubMed/Medline, Scopus, and Web of Science were searched with the terms “STING”, “TBK 1”, “IRF3”, and “cGAS”—alone, or together with “periodontitis”. Current studies produced evidence for using STING-pathway-targeting molecules as part of anticancer therapy, and as vaccine adjuvants against microbial infections; however, the role of the STING/TBK1/IRF3 pathway in periodontal disease pathogenesis is still undiscovered. Understanding the stimulation of the innate immune response by cyclic dinucleotides opens a new approach to host modulation therapies in periodontology.

scholarly journals Molecular diversity of Mycobacterium tuberculosis strains in a slum area of Rio de Janeiro, Brazil

2008 ◽  
Vol 34 (12) ◽  
pp. 1063-1068 ◽  
Author(s):  
Joycenea Matsuda Mendes ◽  
Silvia Maria Almeida Machado ◽  
Maria Cristina Lourenço ◽  
Rosa Maria Carvalho Ferreira ◽  
Leila de Souza Fonseca ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Rio De Janeiro ◽  
Insertion Sequence ◽  
Fragment Length Polymorphism ◽  
Control Program ◽  
Molecular Study ◽  
Tuberculosis Control ◽  
Primary Resistance ◽  
The City ◽  
Insight Into

This retrospective molecular study involving restriction fragment length polymorphism, using insertion sequence 6110 as a marker, was conducted in order to provide an initial insight into the genetic diversity of Mycobacterium tuberculosis strains isolated in the slums of the Complexo de Manguinhos, located in the city of Rio de Janeiro, Brazil. Of the 67 strains evaluated, 23 (34.3%) were found to belong to clusters (total clusters, 10). Household and social chains of transmission were associated with clustering, in 20% and 60%, respectively. Living in the Conjunto Habitacional Programado 2 slum was associated with clustering. Although not significant, it is relevant that 26% of the clustered strains presented primary resistance. These findings, although possibly underestimating the prevalence due to the failure to analyze all strains, could help improve the local tuberculosis control program.

scholarly journals The complex, bidirectional role of extracellular vesicles in infection

2021 ◽  
Author(s):  
Joni Renee White ◽  
Priscila Dauros-Singorenko ◽  
Jiwon Hong ◽  
Frédérique Vanholsbeeck ◽  
Anthony Phillips ◽  
...  
Keyword(s):  
Immune Response ◽  
Extracellular Vesicles ◽  
Bacterial Pathogens ◽  
Host Cells ◽  
Signalling Molecules ◽  
Host Pathogen ◽  
Domains Of Life

Cells from all domains of life release extracellular vesicles (EVs), packages that carry a cargo of molecules that participate in communication, co-ordination of population behaviours, virulence and immune response mechanisms. Mammalian EVs play an increasingly recognised role to fight infection, yet may also be commandeered to disseminate pathogens and enhance infection. EVs released by bacterial pathogens may deliver toxins to host cells, signalling molecules and new DNA to other bacteria, and act as decoys, protecting infecting bacteria from immune killing. In this review, we explore the role of EVs in infection from the perspective of both the pathogen and host, and highlight their importance in the host/pathogen relationship. We highlight proposed strategies for EVs in therapeutics, and call attention to areas where existing knowledge and evidence is lacking.

scholarly journals Review on the Role of Host Immune Response in Protection and Immunopathogenesis during Cutaneous Leishmaniasis Infection

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Teshager Dubie ◽  
Yasin Mohammed
Keyword(s):  
Immune Response ◽  
Cutaneous Leishmaniasis ◽  
Proinflammatory Cytokines ◽  
Parasitic Infection ◽  
Host Immune Response ◽  
Immune Defense ◽  
Host Cells ◽  
Infected Host ◽  
Major Public Health Problem

Cutaneous leishmaniasis (CL) is a major public health problem worldwide and spreads to human via the bite of sand flies during blood meal. Following its inoculation, the promastigotes are immediately taken up by phagocytic cells and these leishmania-infected host cells produce proinflammatory cytokines that activate other immune cells and these infected host cells produce more cytokines and reactive nitrogen and oxygen species for efficient control of leishmania infection. Many experimental studies showed that resistance to infection with leishmania paraites is associated with the production of proinflammatory cytokines and activation of CD4+ Th1 response. On the other hand, vulnerability to this parasitic infection is correlated to production of T helper 2 cytokines that facilitate persistence of parasites and disease progression. In addition, some studies have also indicated that CD8+ T cells play a vital role in immune defense through cytokine production and their cytotoxic activity and excessive production of proinflammatory mediators promote amplified recruitment of cells. This could be correlated with excessive inflammatory reaction and ultimately resulted in tissue destruction and development of immunopathogenesis. Thus, there are contradictions regarding the role of immune responses in protection and immunopathogenesis of CL disease. Therefore, the aim of this paper was to review the role of host immune response in protection and its contribution to disease severity for CL infection. In order to obtain more meaningful data regarding the nature of immune response to leishmania, further in-depth studies focused on immune modulation should be conducted to develop better therapeutic strategies.

scholarly journals PO 8383 THE ROLE OF PLASMA B CELLS IN MYCOBACTERIUM TUBERCULOSIS INFECTION AND DISEASE

2019 ◽  
Vol 4 (Suppl 3) ◽  
pp. A31.2-A31
Author(s):  
Awa Gindeh ◽  
Simon Donkor ◽  
Olumuyiwa Owolabi
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
B Cells ◽  
B Cell ◽  
Bacterial Infections ◽  
Relative Proportion ◽  
Post Treatment ◽  
Latent Tb ◽  
Latent Tb Infection

BackgroundTuberculosis (TB) is still a major global health problem with about one-quarter of the global population infected with the causative pathogen, Mycobacterium tuberculosis (Mtb). The role of T-cells in the adaptive immune response against Mtb has been extensively studied with little information on the role of B-cells. B-cells produce antibodies and differentiate into plasma and memory B-cells. Plasmablasts are a subset of plasma cells only present in the peripheral circulation following an ongoing infection or vaccination. Immunoglobulin G’(IgG) especially IgG2 mounts more efficient immune response against bacterial infections, mainly attributed to the high affinity of IgG2 binding to the Fcγ receptor. Therefore, we hypothesised that Mtb-specific IgG +plasmablasts may be a useful biomarker of TB infection status.MethodsEx-vivo B-cell enzyme-linked immunospot (ELISPOT) was used to identify plasmablasts responses to Mtb-specific antigens ESAT-6/CFP-10 (EC), together with non-specific Mtb purified protein derivative (PPD) and a positive (total IgG) and negative (media only) control from adults with active TB pre- and post-treatment (n=20) or with latent TB infection (LTBI; n=20) in The Gambia.ResultsFrequencies of Mtb-specific plasmablasts were significantly higher in active TB cases pre-treatment compared to post-treatment (p<0.0001) and LTBI with no difference seen following PPD stimulation. Interestingly, total IgG +cells were lower in the cases at recruitment but increased following treatment indicating the relative proportion of Mtb-specific responses were also significantly different (p=0.034) prior to therapy.ConclusionThese data show that B-cell responses are differentially modulated during active and latent TB infection, suggesting that plasmablasts may be a useful biomarker for TB infection in TB-endemic settings.

scholarly journals SLC19A1 is an importer of the immunotransmitter cGAMP

2019 ◽  
Author(s):  
Anthony F. Cordova ◽  
Christopher Ritchie ◽  
Gaelen T. Hess ◽  
Michael C. Bassik ◽  
Lingyin Li
Keyword(s):  
Immune Response ◽  
Clinical Trials ◽  
Cell Membrane ◽  
Cancer Therapeutics ◽  
Host Cells ◽  
Genome Wide ◽  
A Genome ◽  
Crispr Screen ◽  
Sting Pathway ◽  
Insight Into

Abstract2’3’-cyclic-GMP-AMP (cGAMP) is a second messenger that activates the antiviral Stimulator of Interferon Genes (STING) pathway. We recently identified a novel role for cGAMP as a soluble, extracellular immunotransmitter that is produced and secreted by cancer cells. Secreted cGAMP is then sensed by host cells, eliciting an antitumoral immune response. Due to the antitumoral effects of cGAMP, other CDN-based STING agonists are currently under investigation in clinical trials for metastatic solid tumors. However, it is unknown how cGAMP and other CDNs cross the cell membrane to activate intracellular STING. Using a genome-wide CRISPR screen we identified SLC19A1 as the first known importer of cGAMP and other CDNs, including the investigational new drug 2′3′-bisphosphosphothioate-cyclic-di-AMP (2′3′-CDAS). These discoveries will provide insight into cGAMP’s role as an immunotransmitter and aid in the development of more targeted CDN-based cancer therapeutics.

scholarly journals mSphere of Influence: Role of IRGM1 in Disease Control

mSphere ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Sumanta Kumar Naik
Keyword(s):  
Immune Response ◽  
Quality Control ◽  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Disease Control ◽  
Host Immune Response ◽  
Specific Interest ◽  
Mitochondrial Quality Control ◽  
Content Type

ABSTRACT Sumanta K. Naik works in the tuberculosis field, with a specific interest in the host immune response to Mycobacterium tuberculosis infection. In this mSphere of Influence article, he reflects on how the paper “IRGM1 links mitochondrial quality control to autoimmunity” by Prashant Rai et al. (Nat Immunol, 22:312–321, 2021, https://doi.org/10.1038/s41590-020-00859-0) impacted his research by revealing new roles for Irgm1 in immune responses.

scholarly journals The Role of Microbiome in Cancer Cell Stimulation and Therapy

2021 ◽  
pp. 97-115
Author(s):  
Shahira Hassoubah
Keyword(s):  
Immune Response ◽  
Human Microbiome ◽  
Future Research ◽  
Published Data ◽  
Disease States ◽  
Life Threatening ◽  
Indigenous Microbiota ◽  
Symbiotic Microbiota ◽  
Insight Into

In recent times, the microbiome has been increasingly recognized as having a hand in various disease states that include cancer as a part. Our commensal and symbiotic microbiota, in addition to pathogens with oncogenesis features, have tumor-suppressive characteristics. Our nutrition and other environmental influences can modulate some microbial species representatives within our digestive system and other systems. The microbiota has recently shown a two-way link to cancer immunotherapy for both the prognosis and the therapeutic aspects. Preclinical results indicated that microbiota modification could be transformed into a novel technique to improve cancer therapy's effectiveness. This article aimed to review recent development in our understanding of the microbiome and its relationship to cancer cells and discuss how the microbiome stimulates cancer and its clinical and therapeutic applications. Such information was selected and extracted from the PubMed, Web of Science, and Google Scholar databases for published data from 2000 to 2020 using relevant keywords containing a combination of terms, including the microbiome, cancer, immune response, immune response, and microbiota. Finally, we concluded that studying the human microbiome is necessary because it provides a thorough understanding of humans' interaction and their indigenous microbiota. The microbiome provides useful insight into future research studies to optimize these species to fight life-threatening diseases such as cancer and has rendered the microbiome a successful cancer treatment strategy.

Unravelling some mysteries of porcine respiratory and reproductive syndrome virus (PRRSV) infections: new insights from modelling studies

2009 ◽  
Vol 2009 ◽  
pp. 30-30
Author(s):  
A Doeschl-Wilson ◽  
I Kyriazakis ◽  
L Galina-Pantoja
Keyword(s):  
Immune Response ◽  
Host Immune Response ◽  
Growing Pigs ◽  
Modelling Studies ◽  
Porcine Respiratory ◽  
Insight Into

Porcine reproductive and respiratory syndrome (PRRS) is an endemic pig disease in most European countries, causing respiratory distress, fever and growth reductions in growing pigs and increased litter mortality in sows. The disease is characterised by exceptionally long-term viral persistence within the host, a weak innate host immune response and delayed adaptive host immune response, and large between animal variation in the immune response (Murtaugh et al., 2004). Although numerous in-vitro and in-vivo studies produced valid insight into the fine details of the virus dynamics and its interaction with the host’s immune response, several fundamental questions concerning the role of diverse immune components and host genetics remain unanswered. In this study mathematical models were developed to investigate the role of diverse processes caused by the virus or the immune response on the infection characteristics.

scholarly journals Production of Monocyte Chemoattractant Protein 1 in Tuberculosis Patients

1998 ◽  
Vol 66 (5) ◽  
pp. 2319-2322 ◽  
Author(s):  
YuanGuang Lin ◽  
JianHua Gong ◽  
Ming Zhang ◽  
Wanfen Xue ◽  
Peter F. Barnes
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Inflammatory Response ◽  
Lymph Nodes ◽  
Blood Monocytes ◽  
Monocyte Chemoattractant Protein 1 ◽  
Tuberculosis Patients ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein

ABSTRACT To investigate the role of monocyte chemoattractant protein 1 (MCP-1) in the immune response to Mycobacterium tuberculosis, we studied MCP-1 production in tuberculosis patients. CD14+ blood monocytes from tuberculosis patients spontaneously expressed higher levels of MCP-1 mRNA and protein than CD14+ monocytes from healthy tuberculin reactors. MCP-1 production in lymph nodes from tuberculosis patients was also markedly increased. These findings suggest that MCP-1 can contribute to the antimycobacterial inflammatory response by attracting monocytes and T lymphocytes.

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