In-silico Targets in Immune Response

2019 ◽  
pp. 393-402
Author(s):  
Amit Bhattacharya ◽  
Nidhi Sharma ◽  
Neetu Bhattacharya ◽  
Sabyasachi Senapati
Keyword(s):  
Immune Response ◽  
In Silico

scholarly journals Robust Phagocyte Recruitment Controls the Opportunistic Fungal PathogenMucor circinelloidesin Innate GranulomasIn Vivo

mBio ◽  
2018 ◽  
Vol 9 (2) ◽  
Author(s):  
Sarah Inglesfield ◽  
Aleksandra Jasiulewicz ◽  
Matthew Hopwood ◽  
James Tyrrell ◽  
George Youlden ◽  
...  
Keyword(s):  
Immune Response ◽  
Fungal Infection ◽  
Real Time ◽  
Clinical Management ◽  
In Silico ◽  
Innate Immune ◽  
Granuloma Formation ◽  
Early Immune Response ◽  
Latent Stage

ABSTRACTMucormycosis is an emerging fungal infection with extremely high mortality rates in patients with defects in their innate immune response, specifically in functions mediated through phagocytes. However, we currently have a limited understanding of the molecular and cellular interactions between these innate immune effectors and mucormycete spores during the early immune response. Here, the early events of innate immune recruitment in response to infection byMucor circinelloidesspores are modeled by a combinedin silicomodeling approach and real-timein vivomicroscopy. Phagocytes are rapidly recruited to the site of infection in a zebrafish larval model of mucormycosis. This robust early recruitment protects from disease onsetin vivo.In silicoanalysis identified that protection is dependent on the number of phagocytes at the infection site, but not the speed of recruitment. The mathematical model highlights the role of proinflammatory signals for phagocyte recruitment and the importance of inhibition of spore germination for protection from active fungal disease. Thesein silicodata are supported by anin vivolack of fungal spore killing and lack of reactive oxygen burst, which together result in latent fungal infection. During this latent stage of infection, spores are controlled in innate granulomasin vivo. Disease can be reactivated by immunosuppression. Together, these data represent the firstin vivoreal-time analysis of innate granuloma formation during the early stages of a fungal infection. The results highlight a potential latent stage during mucormycosis that should urgently be considered for clinical management of patients.IMPORTANCEMucormycosis is a dramatic fungal infection frequently leading to the death of patients. We know little about the immune response to the fungus causing this infection, although evidence points toward defects in early immune events after infection. Here, we dissect this early immune response to infectious fungal spores. We show that specialized white blood cells (phagocytes) rapidly respond to these spores and accumulate around the fungus. However, we demonstrate that the mechanisms that enable phagocytes to kill the fungus fail, allowing for survival of spores. Instead a cluster of phagocytes resembling an early granuloma is formed around spores to control the latent infection. This study is the first detailed analysis of early granuloma formation during a fungal infection highlighting a latent stage that needs to be considered for clinical management of patients.

scholarly journals An immunoinformatic approach driven by experimental proteomics: in silico design of a subunit candidate vaccine targeting secretory proteins of Leishmania donovani amastigotes

2020 ◽  
Author(s):  
Md Anik Ashfaq Khan ◽  
Jenifar Quaiyum Ami ◽  
Khaledul Faisal ◽  
Rajashree Chowdhury ◽  
Prakash Ghosh ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
In Silico ◽  
Leishmania Donovani ◽  
Methodological Approach ◽  
Receptor Activation ◽  
Dynamics Simulation ◽  
Secretory Proteins ◽  
Binding Interaction ◽  
Binding Interface

Abstract Background Visceral leishmaniasis (VL) caused by dimorphic Leishmania species is a parasitic disease with high socioeconomic burden in endemic areas worldwide. Sustaining control of VL in terms of proper and prevailing immunity development is a global necessity amid unavailability of a prophylactic vaccine. Screening of experimental proteome of the human disease propagating form of Leishmania donovani (amastigote) can be more pragmatic for in silico mining of novel vaccine candidates. Methods By using an immunoinformatic approach, CD4+ and CD8+ T cell-specific epitopes from experimentally reported L. donovani proteins having secretory potential and increased abundance in amastigotes were screened. A chimera linked with a Toll-like receptor 4 (TLR4) peptide adjuvant was constructed and evaluated for physicochemical characteristics, binding interaction with TLR4 in simulated physiological condition and the trend of immune response following hypothetical immunization. Results Selected epitopes from physiologically important L. donovani proteins were found mostly conserved in L. infantum , covering theoretically more than 98% of the global population. The multi-epitope chimeric vaccine was predicted as stable, antigenic and non-allergenic. Structural analysis of vaccine-TLR4 receptor docked complex and its molecular dynamics simulation suggest sufficiently stable binding interface along with prospect of non-canonical receptor activation. Simulation dynamics of immune response following hypothetical immunization indicate active and memory B as well as CD4+ T cell generation potential, and likely chance of a more Th1 polarized response. Conclusions The methodological approach and results from this study could facilitate more informed screening and selection of candidate antigenic proteins for entry into vaccine production pipeline in future to control human VL.

scholarly journals Application of In-Silico Reverse Vaccinology for Designing Multi-Epitope Vaccine Against Coronavirus

2020 ◽  
Author(s):  
Kumar Sharp ◽  
Dr. Shubhangi Dange
Keyword(s):  
Immune Response ◽  
In Silico ◽  
Reverse Vaccinology ◽  
Economic Losses ◽  
The Novel ◽  
Toll Like Receptor ◽  
Ramachandran Plot ◽  
Cell Mediated Immune Response ◽  
Specific Medication ◽  
Novel Coronavirus

In absence of any specific medication or vaccine till now, experimentation has reached new heights. With lockdown imposed in almost every country and huge economic losses the search for a suitable vaccine has still been unsuccessful. In this study we have approached through in-silico method or reverse vaccinology taking advantage of the genome sequence of the novel coronavirus. We created a multi-epitope model vaccine which can elicit both humoral as well as cell-mediated immune response. It is also docked with toll-like receptor 8 TLR-8. The sequence obtained is antigenic, non-allergenic and 86.3% residues are in favourable region of Ramachandran plot. This sequence might have good hope of emerging as the vaccine of the current pandemic if studied more in depth.

In silico analysis revealed Zika virus miRNAs associated with viral pathogenesis through alteration of host genes involved in immune response and neurological functions

2019 ◽  
Vol 91 (9) ◽  
pp. 1584-1594 ◽  
Author(s):  
Md. Sajedul Islam ◽  
Md. Abdullah‐Al‐Kamran Khan ◽  
Md. Wahid Murad ◽  
Marwah Karim ◽  
Abul Bashar Mir Md. Khademul Islam
Keyword(s):  
Immune Response ◽  
Zika Virus ◽  
In Silico ◽  
In Silico Analysis ◽  
Viral Pathogenesis ◽  
Silico Analysis ◽  
Host Genes

scholarly journals Rhipicephalus microplus lipocalins (LRMs): Genomic identification and analysis of the bovine immune response using in silico predicted B and T cell epitopes

2013 ◽  
Vol 43 (9) ◽  
pp. 739-752 ◽  
Author(s):  
Manuel Rodriguez-Valle ◽  
Paula Moolhuijzen ◽  
Emily K. Piper ◽  
Olivia Weiss ◽  
Megan Vance ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
In Silico ◽  
Rhipicephalus Microplus ◽  
T Cell Epitopes

scholarly journals In silico analysis of candidate genes associated with humoral innate immune response in chicken

2011 ◽  
Vol 5 (S4) ◽  
Author(s):  
Anna Slawinska ◽  
Andrzej Witkowski ◽  
Marek Bednarczyk ◽  
Maria Siwek
Keyword(s):  
Immune Response ◽  
Candidate Genes ◽  
Innate Immune Response ◽  
In Silico ◽  
In Silico Analysis ◽  
Innate Immune ◽  
Silico Analysis
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