scholarly journals Mycobacterium tuberculosis LprE enhances bacterial persistence by inhibiting cathelicidin and autophagy in macrophages

2017 ◽  
Author(s):  
Avinash Padhi ◽  
Ella Bhagyaraj ◽  
Mehak Zahoor Khan ◽  
Mainak Biswas ◽  
Srabasti Sengupta ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Signaling Pathway ◽  
Mycobacterium Smegmatis ◽  
Bacterial Survival ◽  
Bacterial Persistence ◽  
Host Immune Responses ◽  
Mycobacterial Pathogenesis

ABSTRACTMycobacterium tuberculosis(Mtb)lipoproteins are known to facilitate bacterial survival by manipulating the host immune responses. Here, we have characterized a novelMtblipoprotein LprE(LprEMtb), and demonstrated its role in mycobacterial survival. LprEMtbacts by down-regulating the expression of cathelicidin, Cyp27B1, VDR and p38-MAPK via TLR-2 signaling pathway. Deletion oflprEMtbresulted in induction of cathelicidin and decreased survival in the host. Interestingly, LprEMtbwas also found to inhibit autophagy mechanism to dampen host immune response. Episomal expression of LprEMtbin non-pathogenicMycobacterium smegmatis(Msm) increased bacillary persistence by down-regulating the expression of cathelicidin and autophagy, while deletion of LprEMtborthologue inMsm, had no effect on cathelicidin and autophagy expression. Moreover, LprEMtbblocked phago-lysosome fusion by suppressing the expression of EEA1, Rab7 and LAMP-1 endosomal markers by down-regulating IL-12 and IL-22 cytokines. Our results indicate that LprEMtbplays an important role in mycobacterial pathogenesis in the context of innate immunity.

scholarly journals β-Catenin Is Required for the cGAS/STING Signaling Pathway but Antagonized by the Herpes Simplex Virus 1 US3 Protein

2019 ◽  
Vol 94 (5) ◽  
Author(s):  
Hongjuan You ◽  
Yingying Lin ◽  
Feng Lin ◽  
Mingyue Yang ◽  
Jiahui Li ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Herpes Simplex ◽  
Immune Responses ◽  
Signaling Pathway ◽  
Kinase Activity ◽  
Dna Virus ◽  
Host Immune Responses ◽  
Simplex Virus ◽  
Antiviral Innate Immunity ◽  
Hsv 1

ABSTRACT The cGAS/STING-mediated DNA-sensing signaling pathway is crucial for interferon (IFN) production and host antiviral responses. Herpes simplex virus I (HSV-1) is a DNA virus that has evolved multiple strategies to evade host immune responses. Here, we demonstrate that the highly conserved β-catenin protein in the Wnt signaling pathway is an important factor to enhance the transcription of type I interferon (IFN-I) in the cGAS/STING signaling pathway, and the production of IFN-I mediated by β-catenin was antagonized by HSV-1 US3 protein via its kinase activity. Infection by US3-deficienct HSV-1 and its kinase-dead variants failed to downregulate IFN-I and IFN-stimulated gene (ISG) production induced by β-catenin. Consistent with this, absence of β-catenin enhanced the replication of US3-deficienct HSV-1, but not wild-type HSV-1. The underlying mechanism was the interaction of US3 with β-catenin and its hyperphosphorylation of β-catenin at Thr556 to block its nuclear translocation. For the first time, HSV-1 US3 has been shown to inhibit IFN-I production through hyperphosphorylation of β-catenin and to subvert host antiviral innate immunity. IMPORTANCE Although increasing evidence has demonstrated that HSV-1 subverts host immune responses and establishes lifelong latent infection, the molecular mechanisms by which HSV-1 interrupts antiviral innate immunity, especially the cGAS/STING-mediated cellular DNA-sensing signaling pathway, have not been fully explored. Here, we show that β-catenin promotes cGAS/STING-mediated activation of the IFN pathway, which is important for cellular innate immune responses and intrinsic resistance to DNA virus infection. The protein kinase US3 antagonizes the production of IFN by targeting β-catenin via its kinase activity. The findings in this study reveal a novel mechanism for HSV-1 to evade host antiviral immunity and add new knowledge to help in understanding the interaction between the host and HSV-1 infection.

scholarly journals The DBL-1/TGF-β signaling pathway regulates pathogen-specific innate immune responses in C. elegans

2021 ◽  
Author(s):  
Bhoomi Madhu ◽  
Tina L. Gumienny
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Signaling Pathway ◽  
Defense Responses ◽  
C Elegans ◽  
Host Immune Responses ◽  
Wide Range ◽  
Independent Functions ◽  
Multiple Cell

Innate immunity in animals is orchestrated by multiple cell signaling pathways, including the TGF-β; superfamily pathway. While the role of TGF-β signaling in innate immunity has been clearly identified, the requirement for this pathway in generating specific, robust responses to different bacterial challenges has not been characterized. Here, we address the role of DBL-1/TGF-β in regulating signature host defense responses to a wide range of bacteria in C. elegans. This work reveals a role of DBL-1/TGF-β in animal survival, organismal behaviors, and molecular responses in different environments. Additionally, we identify a novel role for SMA-4/Smad that suggests both DBL-1/TGF-β-dependent and -independent functions in host avoidance responses. RNA-seq analyses and immunity reporter studies indicate DBL-1/TGF-β differentially regulates target gene expression upon exposure to different bacteria. Furthermore, the DBL-1/TGF-β pathway is itself differentially affected by the bacteria exposure. Collectively, these findings demonstrate bacteria-specific host immune responses regulated by the DBL-1/TGF-β signaling pathway.

scholarly journals Role of Alternative Splicing in Regulating Host Response to Viral Infection

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1720
Author(s):  
Kuo-Chieh Liao ◽  
Mariano A. Garcia-Blanco
Keyword(s):  
Innate Immunity ◽  
Alternative Splicing ◽  
Immune Responses ◽  
Viral Infection ◽  
Rna Splicing ◽  
Type I ◽  
Host Immune Responses ◽  
Transcriptional Regulatory Mechanisms ◽  
Host Virus Interactions

The importance of transcriptional regulation of host genes in innate immunity against viral infection has been widely recognized. More recently, post-transcriptional regulatory mechanisms have gained appreciation as an additional and important layer of regulation to fine-tune host immune responses. Here, we review the functional significance of alternative splicing in innate immune responses to viral infection. We describe how several central components of the Type I and III interferon pathways encode spliced isoforms to regulate IFN activation and function. Additionally, the functional roles of splicing factors and modulators in antiviral immunity are discussed. Lastly, we discuss how cell death pathways are regulated by alternative splicing as well as the potential role of this regulation on host immunity and viral infection. Altogether, these studies highlight the importance of RNA splicing in regulating host–virus interactions and suggest a role in downregulating antiviral innate immunity; this may be critical to prevent pathological inflammation.

scholarly journals Inflammasomes inMycobacterium tuberculosis-Driven Immunity

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Sebastian Wawrocki ◽  
Magdalena Druszczynska
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Inflammatory Response ◽  
Immune Responses ◽  
Proinflammatory Cytokines ◽  
Immune Cells ◽  
Protein Complexes ◽  
Inflammasome Activation ◽  
Host Immune Responses ◽  
Multimeric Protein

The development of effective innate and subsequent adaptive host immune responses is highly dependent on the production of proinflammatory cytokines that increase the activity of immune cells. The key role in this process is played by inflammasomes, multimeric protein complexes serving as a platform for caspase-1, an enzyme responsible for proteolytic cleavage of IL-1βand IL-18 precursors. Inflammasome activation, which triggers the multifaceted activity of these two proinflammatory cytokines, is a prerequisite for developing an efficient inflammatory response against pathogenicMycobacterium tuberculosis(M.tb). This review focuses on the role of NLRP3 and AIM2 inflammasomes inM.tb-driven immunity.

scholarly journals Impact of Influenza A Virus Shutoff Proteins on Host Immune Responses

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 629
Author(s):  
Megan M. Dunagan ◽  
Kala Hardy ◽  
Toru Takimoto
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Influenza A Virus ◽  
Influenza A ◽  
Human Populations ◽  
Lymphocyte Migration ◽  
Host Immune Responses ◽  
Mhc Molecules ◽  
The Impact

Influenza A virus (IAV) is a significant human pathogen that causes seasonal epidemics. Although various types of vaccines are available, IAVs still circulate among human populations, possibly due to their ability to circumvent host immune responses. IAV expresses two host shutoff proteins, PA-X and NS1, which antagonize the host innate immune response. By transcriptomic analysis, we previously showed that PA-X is a major contributor for general shutoff, while shutoff active NS1 specifically inhibits the expression of host cytokines, MHC molecules, and genes involved in innate immunity in cultured human cells. So far, the impact of these shutoff proteins in the acquired immune response in vivo has not been determined in detail. In this study, we analyzed the effects of PA-X and NS1 shutoff activities on immune response using recombinant influenza A/California/04/2009 viruses containing mutations affecting the expression of shutoff active PA-X and NS1 in a mouse model. Our data indicate that the virus without shutoff activities induced the strongest T and B cell responses. Both PA-X and NS1 reduced host immune responses, but shutoff active NS1 most effectively suppressed lymphocyte migration to the lungs, antibody production, and the generation of IAV specific CD4+ and CD8+ T cells. NS1 also prevented the generation of protective immunity against a heterologous virus challenge. These data indicate that shutoff active NS1 plays a major role in suppressing host immune responses against IAV infection.

scholarly journals Extracellular Vesicles from Different Pneumococcal Serotypes Are Internalized by Macrophages and Induce Host Immune Responses

Pathogens ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1530
Author(s):  
Alfonso Olaya-Abril ◽  
Rafael Prados-Rosales ◽  
José A. González-Reyes ◽  
Arturo Casadevall ◽  
Liise-anne Pirofski ◽  
...  
Keyword(s):  
Immune Response ◽  
Biological Activity ◽  
Immune Responses ◽  
Extracellular Vesicles ◽  
Host Cells ◽  
Pneumococcal Serotypes ◽  
Human Pathogen ◽  
Host Immune Responses ◽  
Serotype 1 ◽  
Transient Loss

Bacterial extracellular vesicles are membranous ultrastructures released from the cell surface. They play important roles in the interaction between the host and the bacteria. In this work, we show how extracellular vesicles produced by four different serotypes of the important human pathogen, Streptococcus pneumoniae, are internalized by murine J774A.1 macrophages via fusion with the membrane of the host cells. We also evaluated the capacity of pneumococcal extracellular vesicles to elicit an immune response by macrophages. Macrophages treated with the vesicles underwent a serotype-dependent transient loss of viability, which was further reverted. The vesicles induced the production of proinflammatory cytokines, which was higher for serotype 1 and serotype 8-derived vesicles. These results demonstrate the biological activity of extracellular vesicles of clinically important pneumococcal serotypes.

scholarly journals The Mycobacterium tuberculosis PE_PGRS Protein Family Acts as an Immunological Decoy to Subvert Host Immune Response

2022 ◽  
Vol 23 (1) ◽  
pp. 525
Author(s):  
Tarina Sharma ◽  
Anwar Alam ◽  
Aquib Ehtram ◽  
Anshu Rani ◽  
Sonam Grover ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Current Knowledge ◽  
Immune Effector ◽  
Host Immune Responses ◽  
Intrinsically Disordered ◽  
Multiple Strategies ◽  
Latent Stage ◽  
Immune Mediated ◽  
Critical Edge

Mycobacterium tuberculosis (M.tb) is a successful pathogen that can reside within the alveolar macrophages of the host and can survive in a latent stage. The pathogen has evolved and developed multiple strategies to resist the host immune responses. M.tb escapes from host macrophage through evasion or subversion of immune effector functions. M.tb genome codes for PE/PPE/PE_PGRS proteins, which are intrinsically disordered, redundant and antigenic in nature. These proteins perform multiple functions that intensify the virulence competence of M.tb majorly by modulating immune responses, thereby affecting immune mediated clearance of the pathogen. The highly repetitive, redundant and antigenic nature of PE/PPE/PE_PGRS proteins provide a critical edge over other M.tb proteins in terms of imparting a higher level of virulence and also as a decoy molecule that masks the effect of effector molecules, thereby modulating immuno-surveillance. An understanding of how these proteins subvert the host immunological machinery may add to the current knowledge about M.tb virulence and pathogenesis. This can help in redirecting our strategies for tackling M.tb infections.

scholarly journals Protective and Pathogenic Immune Responses to Cutaneous Leishmaniasis

2021 ◽  
Author(s):  
Elina Panahi ◽  
Danielle I. Stanisic ◽  
Christopher S. Peacock ◽  
Lara J. Herrero
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Cutaneous Leishmaniasis ◽  
Adaptive Immune Response ◽  
Leishmania Parasite ◽  
Host Immune System ◽  
Phagocytic Cells ◽  
Host Immune Responses ◽  
Outcome Severity ◽  
Common Clinical Presentation

Leishmania (Kinetoplastida: Trypanosomatidae) parasites are known to cause a broad spectrum of clinical diseases in humans, collectively known as the leishmaniases. Cutaneous leishmaniasis is the most common clinical presentation with varying degrees of severity largely driven by host immune responses, specifically the interplay between innate and adaptive immune response. The establishment of a T lymphocyte driven cell-mediated immune response, leading to activated phagocytic cells, leading to Leishmania parasite killing and control of infection. Alternatively, the Leishmania parasite manipulates the host immune system, enabling parasite proliferation and clinical disease. Here we review how the cumulative interactions of different aspects of the host immune response determines disease outcome, severity, and immunity to re-infection.

scholarly journals Multiomic Immunophenotyping of COVID-19 Patients Reveals Early Infection Trajectories

2020 ◽  
Author(s):  
Yapeng Su ◽  
Daniel Chen ◽  
Christopher Lausted ◽  
Dan Yuan ◽  
Jongchan Choi ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Surface Proteins ◽  
Host Immune Responses ◽  
Therapeutic Development ◽  
Clinical Measures ◽  
Whole Transcriptome

SUMMARYHost immune responses play central roles in controlling SARS-CoV2 infection, yet remain incompletely characterized and understood. Here, we present a comprehensive immune response map spanning 454 proteins and 847 metabolites in plasma integrated with single-cell multi-omic assays of PBMCs in which whole transcriptome, 192 surface proteins, and T and B cell receptor sequence were co-analyzed within the context of clinical measures from 50 COVID19 patient samples. Our study reveals novel cellular subpopulations, such as proliferative exhausted CD8+ and CD4+ T cells, and cytotoxic CD4+ T cells, that may be features of severe COVID-19 infection. We condensed over 1 million immune features into a single immune response axis that independently aligns with many clinical features and is also strongly associated with disease severity. Our study represents an important resource towards understanding the heterogeneous immune responses of COVID-19 patients and may provide key information for informing therapeutic development.

CD209 (DC-SIGN) – role in the work of the innate immunity and pathogen penetration

2020 ◽  
Vol 1 (9) ◽  
pp. 64-71
Author(s):  
E. A. Klimov ◽  
◽  
E. K. Novitskaya ◽  
S. N. Koval’chuk ◽  
◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Dendritic Cells ◽  
Inflammatory Response ◽  
Signaling Pathway ◽  
Adhesion Molecule ◽  
Immune Evasion ◽  
Intercellular Adhesion Molecule ◽  
Lectin Receptor

Intercellular adhesion molecule CD209 (DC-SIGN) is a membrane C-type lectin receptor expressed on the surface of dendritic cells and macrophages. CD209 plays an important role in innate immunity. Many studies have shown the possibility of interaction of the CD209 molecule with a number of dangerous pathogens of humans and animals. This review summarizes information on the structure of the CD209 gene and its product, describes the role of the CD209 protein in the immune response, in the migration of dendritic cells from the blood to the tissue, and their interaction with neutrophils. The currently known signaling pathway of activation through the CD209 inflammatory response is presented. The role of CD209 as an endocytic antigen receptor and the participation of the protein in immune evasion of pathogens are discussed. The mechanisms known to date for the development of infections caused by pathogens of various nature in animals are described.

Sign in / Sign up

Export Citation Format

Share Document