A possible role for the immune system in adult neurogenesis: new insights from an invertebrate model

The 1st-generation neural precursors in the crustacean brain are functionally analogous to neural stem cells in mammals. Their slow cycling, migration of their progeny, and differentiation of their descendants into neurons over several weeks are features of the neural precursor lineage in crayfish that also characterize adult neurogenesis in mammals. However, the 1st-generation precursors in crayfish do not self-renew, contrasting with conventional wisdom that proposes the long-term self-renewal of adult neural stem cells. Nevertheless, the crayfish neurogenic niche, which contains a total of 200-300 cells, is never exhausted and neurons continue to be produced in the brain throughout the animal's life. The pool of neural precursors in the niche therefore cannot be a closed system, and must be replenished from an extrinsic source. Our in vitro and in vivo data show that cells originating in the innate immune system (but not other cell types) are attracted to and incorporated into the neurogenic niche, and that they express a niche-specific marker, glutamine synthetase. Further, labeled hemocytes that undergo adoptive transfer to recipient crayfish generate cells in neuronal clusters in the olfactory pathway of the adult brain. These hemocyte descendants express appropriate neurotransmitters and project to target areas typical of neurons in these regions. These studies indicate that under natural conditions, the immune system provides neural precursors supporting adult neurogenesis in the crayfish brain, challenging the canonical view that ectodermal tissues generating the embryonic nervous system are the sole source of neurons in the adult brain. However, these are not the first studies that directly implicate the immune system as a source of neural precursor cells. Several types of data in mammals, including adoptive transfers of bone marrow or stem cells as well as the presence of fetal microchimerism, suggest that there must be a population of cells that are able to access the brain and generate new neurons in these species.

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Experimental evolution of immunological specificity

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1904828116 ◽

2019 ◽

Vol 116 (41) ◽

pp. 20598-20604 ◽

Cited By ~ 9

Author(s):

Kevin Ferro ◽

Robert Peuß ◽

Wentao Yang ◽

Philip Rosenstiel ◽

Hinrich Schulenburg ◽

...

Keyword(s):

Immune System ◽

Adaptive Immune System ◽

High Specificity ◽

Immune Memory ◽

Transcriptomic Response ◽

Immune Priming ◽

Immune Genes ◽

Adaptive Immune ◽

Immunological Specificity ◽

Invertebrate Model

Memory and specificity are hallmarks of the adaptive immune system. Contrary to prior belief, innate immune systems can also provide forms of immune memory, such as immune priming in invertebrates and trained immunity in vertebrates. Immune priming can even be specific but differs remarkably in cellular and molecular functionality from the well-studied adaptive immune system of vertebrates. To date, it is unknown whether and how the level of specificity in immune priming can adapt during evolution in response to natural selection. We tested the evolution of priming specificity in an invertebrate model, the beetle Tribolium castaneum. Using controlled evolution experiments, we selected beetles for either specific or unspecific immune priming toward the bacteria Pseudomonas fluorescens, Lactococcus lactis, and 4 strains of the entomopathogen Bacillus thuringiensis. After 14 generations of host selection, specificity of priming was not universally higher in the lines selected for specificity, but rather depended on the bacterium used for priming and challenge. The insect pathogen B. thuringiensis induced the strongest priming effect. Differences between the evolved populations were mirrored in the transcriptomic response, revealing involvement of immune, metabolic, and transcription-modifying genes. Finally, we demonstrate that the induction strength of a set of differentially expressed immune genes predicts the survival probability of the evolved lines upon infection. We conclude that high specificity of immune priming can evolve rapidly for certain bacteria, most likely due to changes in the regulation of immune genes.

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A Common Language: How Neuroimmunological Cross Talk Regulates Adult Hippocampal Neurogenesis

Stem Cells International ◽

10.1155/2016/1681590 ◽

2016 ◽

Vol 2016 ◽

pp. 1-13 ◽

Cited By ~ 14

Author(s):

Odette Leiter ◽

Gerd Kempermann ◽

Tara L. Walker

Keyword(s):

Immune System ◽

Adult Neurogenesis ◽

Immune Cells ◽

Hippocampal Neurogenesis ◽

Adult Brain ◽

Adult Hippocampal Neurogenesis ◽

Normal Brain ◽

Intrinsic Cues ◽

Normal Brain Function ◽

The Brain

Immune regulation of the brain is generally studied in the context of injury or disease. Less is known about how the immune system regulates the brain during normal brain function. Recent work has redefined the field of neuroimmunology and, as long as their recruitment and activation are well regulated, immune cells are now known to have protective properties within the central nervous system in maintaining brain health. Adult neurogenesis, the process of new neuron generation in the adult brain, is highly plastic and regulated by diverse extrinsic and intrinsic cues. Emerging research has shown that immune cells and their secreted factors can influence adult neurogenesis, both under baseline conditions and during conditions known to change neurogenesis levels, such as aging and learning in an enriched environment. This review will discuss how, under nonpathological conditions, the immune system can interact with the neural stem cells to regulate adult neurogenesis with particular focus on the hippocampus—a region crucial for learning and memory.

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Parasite Evolution and the Immune System

Allergy & Clinical Immunology International - Journal of the World Allergy Organization ◽

10.1027/0838-1925.17.6.229 ◽

2005 ◽

Vol 17 (06) ◽

pp. 229-236

Author(s):

Kathleen Barnes

Keyword(s):

Immune System ◽

Parasite Evolution

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Learned Placebo Effects in the Immune System

Zeitschrift für Psychologie ◽

10.1027/2151-2604/a000184 ◽

2014 ◽

Vol 222 (3) ◽

pp. 148-153 ◽

Cited By ~ 2

Author(s):

Sabine Vits ◽

Manfred Schedlowski

Keyword(s):

Nervous System ◽

Immune System ◽

Associative Learning ◽

Placebo Response ◽

Immunosuppressive Drug ◽

Immune Functions ◽

Placebo Effects ◽

New Therapeutic Approaches ◽

Biological Variables ◽

Experimental Approaches

Associative learning processes are one of the major neuropsychological mechanisms steering the placebo response in different physiological systems and end organ functions. Learned placebo effects on immune functions are based on the bidirectional communication between the central nervous system (CNS) and the peripheral immune system. Based on this “hardware,” experimental evidence in animals and humans showed that humoral and cellular immune functions can be affected by behavioral conditioning processes. We will first highlight and summarize data documenting the variety of experimental approaches conditioning protocols employed, affecting different immunological functions by associative learning. Taking a well-established paradigm employing a conditioned taste aversion model in rats with the immunosuppressive drug cyclosporine A (CsA) as an unconditioned stimulus (US) as an example, we will then summarize the efferent and afferent communication pathways as well as central processes activated during a learned immunosuppression. In addition, the potential clinical relevance of learned placebo effects on the outcome of immune-related diseases has been demonstrated in a number of different clinical conditions in rodents. More importantly, the learned immunosuppression is not restricted to experimental animals but can be also induced in humans. These data so far show that (i) behavioral conditioned immunosuppression is not limited to a single event but can be reproduced over time, (ii) immunosuppression cannot be induced by mere expectation, (iii) psychological and biological variables can be identified as predictors for this learned immunosuppression. Together with experimental approaches employing a placebo-controlled dose reduction these data provide a basis for new therapeutic approaches to the treatment of diseases where a suppression of immune functions is required via modulation of nervous system-immune system communication by learned placebo effects.

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