Characterization of cross-reactive immune responses in the context of a complex host-pathogen system

2018 ◽  
Author(s):  
Karina Pires de Sousa
Keyword(s):  
Immune Responses ◽  
Host Pathogen

scholarly journals Dual RNA-Seq Enables Full-Genome Assembly of Measles Virus and Characterization of Host–Pathogen Interactions

2021 ◽  
Vol 9 (7) ◽  
pp. 1538
Author(s):  
Timokratis Karamitros ◽  
Vasiliki Pogka ◽  
Gethsimani Papadopoulou ◽  
Ourania Tsitsilonis ◽  
Maria Evangelidou ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Infection ◽  
Peripheral Blood ◽  
Measles Virus ◽  
Full Genome ◽  
Rna Seq ◽  
Host Pathogen Interactions ◽  
Dnase Treatment ◽  
Host Pathogen

Measles virus (MeV) has a negative-sense 15 kb long RNA genome, which is generally conserved. Recent advances in high-throughput sequencing (HTS) and Dual RNA-seq allow the analysis of viral RNA genomes and the discovery of viral infection biomarkers, via the simultaneous characterization of the host transcriptome. However, these host–pathogen interactions remain largely unexplored in MeV infections. We performed untargeted Dual RNA-seq in 6 pharyngeal and 6 peripheral blood mononuclear cell (PBMCs) specimens from patients with MeV infection, as confirmed via routine real-time PCR testing. Following optimised DNase treatment of total nucleic acids, we used the pharyngeal samples to build poly-A-enriched NGS libraries. We reconstructed the viral genomes using the pharyngeal datasets and we further conducted differential expression, gene-ontology and pathways enrichment analysis to compare both the pharyngeal and the peripheral blood transcriptomes of the MeV-infected patients vs. control groups of healthy individuals. We obtained 6 MeV genotype-B3 full-genome sequences. We minutely analyzed the transcriptome of the MeV-infected pharyngeal epithelium, detecting all known viral infection biomarkers, but also revealing a functional cluster of local antiviral and inflammatory immune responses, which differ substantially from those observed in the PBMCs transcriptome. The application of Dual RNA-seq technologies in MeV-infected patients can potentially provide valuable information on the virus genome structure and the cellular innate immune responses and drive the discovery of new targets for antiviral therapy.

scholarly journals Butyrophilin-like 2 regulates site-specific adaptations of intestinal γδ intraepithelial lymphocytes

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Casandra Panea ◽  
Ruoyu Zhang ◽  
Jeffrey VanValkenburgh ◽  
Min Ni ◽  
Christina Adler ◽  
...  
Keyword(s):  
Immune Responses ◽  
Intraepithelial Lymphocytes ◽  
Homeostatic Proliferation ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Site Specific ◽  
Adaptive Immune ◽  
Intestinal Segments ◽  
Repertoire Diversity

AbstractTissue-resident γδ intraepithelial lymphocytes (IELs) orchestrate innate and adaptive immune responses to maintain intestinal epithelial barrier integrity. Epithelia-specific butyrophilin-like (Btnl) molecules induce perinatal development of distinct Vγ TCR+ IELs, however, the mechanisms that control γδ IEL maintenance within discrete intestinal segments are unclear. Here, we show that Btnl2 suppressed homeostatic proliferation of γδ IELs preferentially in the ileum. High throughput transcriptomic characterization of site-specific Btnl2-KO γδ IELs reveals that Btnl2 regulated the antimicrobial response module of ileal γδ IELs. Btnl2 deficiency shapes the TCR specificities and TCRγ/δ repertoire diversity of ileal γδ IELs. During DSS-induced colitis, Btnl2-KO mice exhibit increased inflammation and delayed mucosal repair in the colon. Collectively, these data suggest that Btnl2 fine-tunes γδ IEL frequencies and TCR specificities in response to site-specific homeostatic and inflammatory cues. Hence, Btnl-mediated targeting of γδ IEL development and maintenance may help dissect their immunological functions in intestinal diseases with segment-specific manifestations.

scholarly journals The Role of Macrophages in the Host’s Defense against Sporothrix schenckii

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 905
Author(s):  
Estela Ruiz-Baca ◽  
Armando Pérez-Torres ◽  
Yolanda Romo-Lozano ◽  
Daniel Cervantes-García ◽  
Carlos A. Alba-Fierro ◽  
...  
Keyword(s):  
Immune Responses ◽  
Macrophage Polarization ◽  
Sporothrix Schenckii ◽  
Macrophage Cell ◽  
Cell Recruitment ◽  
Host Pathogen Interaction ◽  
Interaction Processes ◽  
Host Pathogen ◽  
Molecular Patterns

The role of immune cells associated with sporotrichosis caused by Sporothrix schenckii is not yet fully clarified. Macrophages through pattern recognition receptors (PRRs) can recognize pathogen-associated molecular patterns (PAMPs) of Sporothrix, engulf it, activate respiratory burst, and secrete pro-inflammatory or anti-inflammatory biological mediators to control infection. It is important to consider that the characteristics associated with S. schenckii and/or the host may influence macrophage polarization (M1/M2), cell recruitment, and the type of immune response (1, 2, and 17). Currently, with the use of new monocyte-macrophage cell lines, it is possible to evaluate different host–pathogen interaction processes, which allows for the proposal of new mechanisms in human sporotrichosis. Therefore, in order to contribute to the understanding of these host–pathogen interactions, the aim of this review is to summarize and discuss the immune responses induced by macrophage-S. schenckii interactions, as well as the PRRs and PAMPs involved during the recognition of S. schenckii that favor the immune evasion by the fungus.

scholarly journals Development of Neutralizing Monoclonal Antibodies for Oncogenic Human Papillomavirus Types 31, 33, 45, 52, and 58

2014 ◽  
Vol 21 (4) ◽  
pp. 587-593 ◽  
Author(s):  
Martha J. Brown ◽  
Hanna Seitz ◽  
Victoria Towne ◽  
Martin Müller ◽  
Adam C. Finnefrock
Keyword(s):  
Monoclonal Antibodies ◽  
Human Papillomavirus ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Cervical Cancers ◽  
Hpv Types ◽  
Oncogenic Hpv ◽  
Neutralizing Epitopes ◽  
Selection Of

ABSTRACTHuman papillomavirus (HPV) is the etiological agent for all cervical cancers, a significant number of other anogenital cancers, and a growing number of head and neck cancers. Two licensed vaccines offer protection against the most prevalent oncogenic types, 16 and 18, responsible for approximately 70% of cervical cancer cases worldwide and one of these also offers protection against types 6 and 11, responsible for 90% of genital warts. The vaccines are comprised of recombinantly expressed major capsid proteins that self-assemble into virus-like particles (VLPs) and prevent infection by eliciting neutralizing antibodies. Adding the other frequently identified oncogenic types 31, 33, 45, 52, and 58 to a vaccine would increase the coverage against HPV-induced cancers to approximately 90%. We describe the generation and characterization of panels of monoclonal antibodies to these five additional oncogenic HPV types, and the selection of antibody pairs that were high affinity and type specific and recognized conformation-dependent neutralizing epitopes. Such characteristics make these antibodies useful tools for monitoring the production and potency of a prototype vaccine as well as monitoring vaccine-induced immune responses in the clinic.

scholarly journals Scaling laws describe memories of host–pathogen riposte in the HIV population

2015 ◽  
Vol 112 (7) ◽  
pp. 1965-1970 ◽  
Author(s):  
John P. Barton ◽  
Mehran Kardar ◽  
Arup K. Chakraborty
Keyword(s):  
Neural Networks ◽  
Immune Responses ◽  
Scaling Laws ◽  
Mechanistic Model ◽  
Solvable Model ◽  
Effective Control ◽  
Immune Selection ◽  
Exactly Solvable ◽  
Host Pathogen ◽  
Human Immune

The enormous genetic diversity and mutability of HIV has prevented effective control of this virus by natural immune responses or vaccination. Evolution of the circulating HIV population has thus occurred in response to diverse, ultimately ineffective, immune selection pressures that randomly change from host to host. We show that the interplay between the diversity of human immune responses and the ways that HIV mutates to evade them results in distinct sets of sequences defined by similar collectively coupled mutations. Scaling laws that relate these sets of sequences resemble those observed in linguistics and other branches of inquiry, and dynamics reminiscent of neural networks are observed. Like neural networks that store memories of past stimulation, the circulating HIV population stores memories of host–pathogen combat won by the virus. We describe an exactly solvable model that captures the main qualitative features of the sets of sequences and a simple mechanistic model for the origin of the observed scaling laws. Our results define collective mutational pathways used by HIV to evade human immune responses, which could guide vaccine design.

Characterization of four Toll related genes during development and immune responses in Anopheles gambiae

2002 ◽  
Vol 32 (9) ◽  
pp. 1171-1179 ◽  
Author(s):  
Coralia Luna ◽  
Xuelan Wang ◽  
Yaming Huang ◽  
Jian Zhang ◽  
Liangbiao Zheng
Keyword(s):  
Immune Responses ◽  
Anopheles Gambiae

scholarly journals In depth characterization of vaccine breakthrough infections with SARS-CoV-2 among healthcare workers of a Dutch academic medical center

2021 ◽  
Author(s):  
Lidewij W Rümke ◽  
Femke C Groenveld ◽  
Yvonne M G van Os ◽  
Patrique Praest ◽  
Anniek A N Tanja ◽  
...  
Keyword(s):  
Immune Responses ◽  
Healthcare Workers ◽  
Medical Center ◽  
Academic Medical Center ◽  
Risk Exposure ◽  
Live Virus ◽  
Viral Loads ◽  
Academic Medical ◽  
T Cell Immune Responses

Abstract SARS-CoV-2 infection after COVID-19 vaccination raises concerns about the emergence of vaccine escape variants. Here we characterize 14 breakthrough infections among 5860 fully vaccinated Dutch healthcare workers ≥14 days post final dose of vaccination with either BNT162b2, mRNA-1273 or Ad26.COV2.S. These breakthrough infections presented with regular B.1.1.7 (Alpha) and B.1.617.2 (Delta) variants and high viral loads, despite normal vaccine induced B- and T-cell immune responses detected by live virus neutralization assays and ELISpot. High-risk exposure settings, such as in households, indicate a potential risk of viral transmission despite full vaccination.

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