scholarly journals Natural variation in the contribution of microbial density to inducible immune dynamics

2019 ◽  
Author(s):  
Derrick Jent ◽  
Abby Perry ◽  
Justin Critchlow ◽  
Ann T. Tate
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Natural Variation ◽  
Temporal Dynamics ◽  
Acute Infection ◽  
Theoretical Dependence ◽  
System Evolution ◽  
Immune System Evolution ◽  
Imd Pathway ◽  
Microbial Density

AbstractImmune responses evolve to balance the benefits of microbial killing against the costs of autoimmunity and energetic resource use. Models that explore the evolution of optimal immune responses generally include a term for constitutive immunity, or the level of immunological investment prior to microbial exposure, and for inducible immunity, or investment in immune function after microbial challenge. However, studies rarely consider the functional form of inducible immune responses with respect to microbial density, despite the theoretical dependence of immune system evolution on microbe-versus immune-mediated damage to the host. In this study, we analyze antimicrobial peptide (AMP) gene expression from seven wild-caught flour beetle populations (Tribolium spp.) during acute infection with the virulent bacteria Bacillus thuringiensis (Bt) and Photorhabdus luminescens (P.lum) to demonstrate that inducible immune responses mediated by the humoral IMD pathway exhibit natural variation in both microbe density-dependent and independent temporal dynamics. Beetle populations that exhibited greater AMP expression sensitivity to Bt density were also more likely to die from infection, while populations that exhibited higher microbe density-independent AMP expression were more likely to survive P. luminescens infection. Reduction in pathway signaling efficiency through RNAi-mediated knockdown of the imd gene reduced the magnitude of both microbe-independent and dependent responses and reduced host resistance to Bt growth, but had no net effect on host survival. This study provides a framework for understanding natural variation in the flexibility of investment in inducible immune responses and should inform theory on the contribution of non-equilibrium host-microbe dynamics to immune system evolution.

scholarly journals Evolution of animal immunity in the light of beneficial symbioses

2020 ◽  
Vol 375 (1808) ◽  
pp. 20190601 ◽  
Author(s):  
Nicole M. Gerardo ◽  
Kim L. Hoang ◽  
Kayla S. Stoy
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Host Immune System ◽  
System Evolution ◽  
Symbiotic Associations ◽  
Host Immune Responses ◽  
Immune System Evolution ◽  
System Maintenance ◽  
Key Aspects ◽  
Host Evolution

Immune system processes serve as the backbone of animal defences against pathogens and thus have evolved under strong selection and coevolutionary dynamics. Most microorganisms that animals encounter, however, are not harmful, and many are actually beneficial. Selection should act on hosts to maintain these associations while preventing exploitation of within-host resources. Here, we consider how several key aspects of beneficial symbiotic associations may shape host immune system evolution. When host immunity is used to regulate symbiont populations, there should be selection to evolve and maintain targeted immune responses that recognize symbionts and suppress but not eliminate symbiont populations. Associating with protective symbionts could relax selection on the maintenance of redundant host-derived immune responses. Alternatively, symbionts could facilitate the evolution of host immune responses if symbiont-conferred protection allows for persistence of host populations that can then adapt. The trajectory of immune system evolution will likely differ based on the type of immunity involved, the symbiont transmission mode and the costs and benefits of immune system function. Overall, the expected influence of beneficial symbiosis on immunity evolution depends on how the host immune system interacts with symbionts, with some interactions leading to constraints while others possibly relax selection on immune system maintenance. This article is part of the theme issue ‘The role of the microbiome in host evolution’.

scholarly journals Imd pathway-specific immune assays reveal NF-κB stimulation by viral RNA PAMPs in Aedes aegypti Aag2 cells

2020 ◽  
Author(s):  
Tiffany A. Russell ◽  
Andalus Ayaz ◽  
Andrew D. Davidson ◽  
Ana Fernandez-Sesma ◽  
Kevin Maringer
Keyword(s):  
Immune System ◽  
Aedes Aegypti ◽  
Immune Responses ◽  
Health Impact ◽  
Global Public Health ◽  
Toll Pathway ◽  
Experimental Conditions ◽  
Imd Pathway ◽  
Arboviral Diseases ◽  
Transgenic Insects

ABSTRACTBackgroundThe mosquito Aedes aegypti is a major vector for the arthropod-borne viruses (arboviruses) chikungunya, dengue, yellow fever and Zika viruses. Vector immune responses pose a major barrier to arboviral transmission, and transgenic insects with altered immunity have been proposed as tools for reducing the global public health impact of arboviral diseases. However, a better understanding of virus-immune interactions is needed to progress the development of such transgenic insects. Although the NF-κB-regulated Toll and ‘immunodeficiency’ (Imd) pathways are increasingly thought to be antiviral, relevant pattern recognition receptors (PRRs) and pathogen-associated molecular patterns (PAMPs) remain poorly characterised in A. aegypti.Methodology/Principle FindingsWe developed novel RT-qPCR and luciferase reporter assays to measure induction of the Toll and Imd pathways in the commonly used A. aegypti-derived Aag2 cell line. We thus determined that the Toll pathway is not inducible by exogenous stimulation with bacterial, viral or fungal stimuli in Aag2 cells under our experimental conditions. We used our Imd pathway-specific assays to demonstrate that the viral dsRNA mimic poly(I:C) is sensed by the Imd pathway, likely through intracellular and extracellular PRRs. The Imd pathway was also induced during infection with the model insect-specific virus cricket paralysis virus (CrPV).Conclusions/SignificanceOur demonstration that a general PAMP shared by many arboviruses is sensed by the Imd pathway paves the way for future studies to determine how viral RNA is sensed by mosquito PRRs at a molecular level. Our data also suggest that studies measuring inducible immune pathway activation through antimicrobial peptide (AMP) expression in Aag2 cells should be interpreted cautiously given that the Toll pathway is not responsive under all experimental conditions. With no antiviral therapies and few effective vaccines available to treat arboviral diseases, our findings provide new insights relevant to the development of transgenic mosquitoes as a means of reducing arbovirus transmission.AUTHOR SUMMARYThe mosquito Aedes aegypti, found globally across the tropics and subtropics, transmits viral diseases with a significant global public health impact, including chikungunya, dengue, yellow fever and Zika viruses. There are no antiviral drugs to treat these diseases and few effective vaccines. One way of reducing the global burden of mosquito-borne diseases would be to develop genetically modified mosquitoes unable to transmit viruses. One approach would be to alter the mosquitoes’ immune system to allow them to better fight viral infections. To do so, we first need to understand how viruses are detected by the mosquito immune system. We developed new methods of measuring immune responses in laboratory-cultured mosquito cells and used them to show that one specific arm of the immune system, called the ‘Imd pathway’, can detect the RNA that constitutes the genome of mosquito-borne viruses. These findings pave the way for future immune studies that could inform the development of transmission-incompetent mosquitoes. We also found that another arm of the immune system, called the ‘Toll pathway’, is not functional under any experimental conditions used in this study. This finding has implications for how different laboratories interpret data from these particular cultured cells.

scholarly journals Chronic microbial infections: Manipulation of host immunity as interventional approach

1970 ◽  
Vol 1 (1) ◽  
pp. 13-19
Author(s):  
Sheikh Mohammad Fazle Akbar ◽  
Md Sakirul Islam Khan ◽  
Shunji Mishiro
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Viral Infections ◽  
Inflammatory Diseases ◽  
Acute Infection ◽  
Immune Surveillance ◽  
Host Immune System ◽  
Related Factors ◽  
Chronic Viral Infections ◽  
Microbial Infections

Chronic viral infections represent major challenges in contemporary medicine, virology and pharmacology. The virus-bearing hosts are commonly found in every parts of the world and it is extremely difficult to manage these patients. In addition, considerable numbers of these patients develop progressive diseases and severe complications. Finally, most of these patients act as permanent reservoirs of virus. Understandings of viral life cycle during the last decade of 20th century and the first decade of 21st century have allowed development of hundreds of antiviral agents for different diseases. But, the clinical efficacy of these drugs is not yet satisfactory. In addition, virologists have provided conclusive evidences suggesting that eradication of most chronic virus from infected hosts may an unachievable goal. In this context, it is essential to develop alternative, novel, and evidence-based therapeutic maneuver for these patients. Manipulation of host immune system may be one of these approaches. We would discuss about scopes, limitations, and strategies for manipulation for controlling of chronic viral infections. The primary function of the host's immune system is to mount responses that protect the individual from various microbial infections including viruses. Host's immune responses also control the spread and virulence of the viruses [1]. This is applicable to viruses that cause acute infection. After entering the hosts, these viruses are localized in host's tissues, proliferate and induce antiviral immunity. These cellular events may cause damage and destruction of tissues and the host exhibit features of acute inflammatory diseases. However, the viruses are either almost completely eliminated from the hosts or adequately controlled in situ by host's immune systems. However, chronic infection is established by many viruses because the hosts induce improper and uncoordinated immune responses against these viruses. Most viruses cause persistent infection by evading the host immune surveillance mechanism. Both virus-related factors and host-dependent factors are primarily responsible for viral persistency in subjects with chronic viral infections.    doi: 10.3329/blj.v1i1.2620 Bangladesh Liver Journal Vol.1(1) 2009 p.13-19 

scholarly journals Grammatical Immune System Evolution for Reverse Engineering Nonlinear Dynamic Bayesian Models

2008 ◽  
Vol 6 ◽  
pp. CIN.S694 ◽  
Author(s):  
B.A. McKinney ◽  
D. Tian
Keyword(s):  
Time Series ◽  
Immune System ◽  
Nonlinear Dynamic ◽  
Dynamic Models ◽  
Time Series Data ◽  
Nonlinear System Identification ◽  
Series Data ◽  
Estrogen Metabolism ◽  
System Evolution ◽  
Immune System Evolution

An artificial immune system algorithm is introduced in which nonlinear dynamic models are evolved to fit time series of interacting biomolecules. This grammar-based machine learning method learns the structure and parameters of the underlying dynamic model. In silico immunogenetic mechanisms for the generation of model-structure diversity are implemented with the aid of a grammar, which also enforces semantic constraints of the evolved models. The grammar acts as a DNA repair polymerase that can identify recombination and hypermutation signals in the antibody (model) genome. These signals contain information interpretable by the grammar to maintain model context. Grammatical Immune System Evolution (GISE) is applied to a nonlinear system identification problem in which a generalized (nonlinear) dynamic Bayesian model is evolved to fit biologically motivated artificial time-series data. From experimental data, we use GISE to infer an improved kinetic model for the oxidative metabolism of 17β-estradiol (E2), the parent hormone of the estrogen metabolism pathway.

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