Brain-immune interactions and the neural basis of disease-avoidant ingestive behaviour - PubMed (original) (raw)

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Brain-immune interactions and the neural basis of disease-avoidant ingestive behaviour

Gustavo Pacheco-López et al. Philos Trans R Soc Lond B Biol Sci. 2011.

Abstract

Neuro-immune interactions are widely manifested in animal physiology. Since immunity competes for energy with other physiological functions, it is subject to a circadian trade-off between other energy-demanding processes, such as neural activity, locomotion and thermoregulation. When immunity is challenged, this trade-off is tilted to an adaptive energy protecting and reallocation strategy that is identified as 'sickness behaviour'. We review diverse disease-avoidant behaviours in the context of ingestion, indicating that several adaptive advantages have been acquired by animals (including humans) during phylogenetic evolution and by ontogenetic experiences: (i) preventing waste of energy by reducing appetite and consequently foraging/hunting (illness anorexia), (ii) avoiding unnecessary danger by promoting safe environments (preventing disease encounter by olfactory cues and illness potentiation neophobia), (iii) help fighting against pathogenic threats (hyperthermia/somnolence), and (iv) by associative learning evading specific foods or environments signalling danger (conditioned taste avoidance/aversion) and/or at the same time preparing the body to counteract by anticipatory immune responses (conditioning immunomodulation). The neurobiology behind disease-avoidant ingestive behaviours is reviewed with special emphasis on the body energy balance (intake versus expenditure) and an evolutionary psychology perspective.

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Figures

Figure 1.

Figure 1.

Appetitive and consummatory behaviours are significantly affected by the immune-derived molecules elicited by peripheral immune challenge resulting in innate and learned disease-avoidant ingestive behaviours. Such avoidant behaviours are the result of phylogenetic evolution and ontogenetic experiences with the ultimate goals of: (i) preventing waste of energy, (ii) avoiding unnecessary danger by promoting safe environments, (iii) helping to fight against pathogenic threats, and (iv) by associative learning it may also be possible to evade specific foods or environments signalling danger and/or at the same time prepare the body to counteract by anticipatory immune responses.

Figure 2.

Figure 2.

Neurobiology of disease-avoidant ingestive behaviours. The vagus nerve provides the major neural pathway identified to date. From bottom to top, the initial chemosensory transduction events occur in immune cells that respond to specific chemical components expressed by dangerous micro-organisms. Afterwards in a paracrine-like manner, a close interaction of lymphocytes with sensory neurons bearing appropriate immune-transmitter receptors (e.g. cytokines, prostaglandins, neurotransmitters) leads to viscera–sensory afferent neural signalling [24,30]. This neural pathway is complemented by a humoral afferent pathway (dotted line) involving access of immune-generated molecules throughout circumventricular organs and/or being transduced within the brain perivascular space (see figure 3). In general, the hypothalamus and the nucleus of the solitary tract are constantly involved in processing visceral–immune signalling, being two key neural integrators of energy homeostasis (e.g. appetite, thermoregulation, sleep; reproduction [31]). Besides these structures, two cortico-limbic structures are of relevance within neuro–immune interactions; the insular cortex and the amygdala, being neural nuclei responsible for: (i) stimuli hedonic categorization, (ii) emotionality, and (iii) associative learning, in animals as well as in humans [–36]. Another important sensory route used to avoid sick individuals or contaminated food is the olfactory system. Specific vomeronasal receptors are capable of detecting volatile molecules derived from activated leucocytes and also from pathogens [37]. From top to bottom, this sensory activation would modulate behaviour through canonical olfactory relays in the olfactory bulb, pyriniform cortex and hypothalamus.

Figure 3.

Figure 3.

Pericerebral neuro–immune interactions. Immune-transmitters can cross the blood–brain barrier or originate a second wave of diffusible messengers within the brain parenchyma [26,38,39]. Cytokines or prostaglandin locally produced by endothelial cells or perivascular microglia can activate neurons that project to specific brain areas or diffuse into the brain parenchyma to reach their targets. Thus, activation of neurons can be direct or indirect and potentially occurs in the whole brain. However, receptors relevant for neuro–immune communication in the brain are preferentially located in the vicinity of circumventricular organs, from which the signal is relayed to other brain regions through neuron-to-neuron comunication. IL, interleukin; LPS, lipopolysaccharide; PG, prostaglandins; TNF, tumour necrosis factor.

Figure 4.

Figure 4.

Circadian fuel allocation. During the day (a) many aspects of immune function are inhibited due to the immunosuppressive effects of cortisol and noradrenaline. In contrast at midnight (b), the level of these hormones is low, but growth hormone, prolactin and melatonin are secreted shortly after sleep onset, which activates the immune cells [10]. A tight circadian allocation of fuel is accomplished to cover energy demands optimally. However, when immunity is compromised an ‘_energy demand reaction_’ is elicited by leucocytes mobilizing fuel stocks and supressing demand from other organs/systems, with the overall purpose of preferentially allocating fuels to activated immune cells. Concomitant behavioural changes prevent waste of energy, avoid unnecessary danger and promote safe environments, but at the same time help fight against pathogenic threats; if they survived, the individual would probably form associative memories to anticipate similar threats and/or to counteract inevitable future encounters.

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