A new vision of immunity homeostasis of the superorganism

A new vision of immunity homeostasis of the superorganism

Mucosal Immunology (2010) 3, 450–460

The immune system is commonly perceived as an army of organs, tissues, cells, and molecules that protect from disease by eliminating pathogens. However, as in human society, a clear definition of good and evil might be sometimes difficult to achieve. Not only do we live in contact with a multitude of microbes, but we also live with billions of symbionts that span all the shades from mutualists to potential killers. Together, we compose a superorganism that is capable of optimal living. In that context, the immune system is not a killer, but rather a force that shapes homeostasis within the superorganism.

The capacity to discriminate between good and evil is crucial for survival. Our senses inform us on the nature of the environment and generate negative feelings of fear and disgust, or positive feelings of comfort and love. Accordingly, decisions are taken to follow a secure path. Societies have developed vast cultures to define good and evil to guarantee the survival of the system

The Superorganism

The role of the symbiotic microbiota

The human intestine hosts an astronomical 10¹⁴ bacteria, roughly 100 times the number of cells in our body, and close to 1000 distinct species, not taking in account archea, fungi, and viruses. This microbiota is usually termed commensal, even though there is a considerable degree of mutualism with the host . The microbes benefit from a selective environment that is regularly flooded with nutrients, and the host benefits from microbial activity that complements its digestive pathways, degrades xenobiotics, regulates epithelial homeostasis, and provides a barrier against potential pathogens. Microbial communities reside on all body surfaces, including the entire length of the digestive tract, the vagina, and the skin. Altogether, the partnership of the host with its microbiota can be described as a new functional entity termed a superorganism . This superorganism encodes ~2 × 10⁴ host genes and an estimated ~10⁶ microbial genes, and in addition to the mammalian metabolic pathways, operates a plethora of microbial metabolic pathways collectively termed the metabolome.

The superorganism. In the context discussed here, the superorganism is the composite of a host with its symbiotic microbiota. These two worlds have evolved to live together and establish an equilibrium that optimizes the fitness of the superorganism, and thereby the fitness of both the host and the members of the microbiota. The microbial metabolome¹⁹ complements the mammalian metabolome in a number of functions best described in the intestine whereas the mammalian metabolome forms a niche that allows survival of selected microbes.

the immune system must have co-evolved with the microbiota to adjust its reactivity and maintain homeostasis of the superorganism. In conclusion, the dualistic view that separates the host from its microbiota is of course valid in terms of separation of the genomes, but appears to be overruled at the functional level in the superorganism.

The superorganism

The host and its symbiotic microbiota constitute a superorganism with superior efficiency in digestion, defense, and detoxification, to list a few items, as compared with the bare host (Figure 1). Many systems are actually affected in germfree mice, and therefore, the concept of superorganism is largely validated. Importantly the intestinal microbiota not only affects the intestine but also more distant organs, such as the pancreas, and the hypothalamic–pituitary–adrenal axis during stress response in mice. The mechanism leading to such effects is still a matter of speculation, but a recent paper shows that microbiota-derived peptidoglycans are present in the serum and bone marrow where they enhance neutrophil function. Thus, it is predicted, and testable, that homeostasis of the superorganism not only requires an extensive local crosstalk between symbionts and the immune system, but also a more general systemic effect of microbiota based on invaders or circulating MAMPs

 

The superorganism requires forces, such as the immune system, to maintain homeostasis. During pathogenesis, the equilibrium between the microbiota and the immune system can become dangerously unstable and glide toward collapse and death of the superorganism. In that context, it appears important to decipher the cellular and molecular crosstalk between the symbiotic microbiota, the host, and its immune system. The molecular messengers of this crosstalk may lead to a new generation of preventive and therapeutic avenues: it will be possible to diagnose and understand ruptures of homeostasis, elaborate strategies to prevent progression to disease, and design therapies for return to homeostasis.

Superorganism

Originated from the Latin word supra, meaning “above”, and the Greek word organon, meaning “organ, instrument, tool”. In biology, an organism is a living system capable of autonomous metabolism and reproduction. A superorganism is a living system of a superior degree of complexity, consisting of many organisms. It may be defined more generally as a “collection of agents that can act in concert to produce phenomena governed by the collective”. Examples of superorganisms include ants and termite societies.

Commensalism

Originated from the Latin word cum mensa, meaning “sharing a table”. A relationship between two organisms where one organism benefits but the other is unaffected. Microbes that expand in the intestine obviously benefit from the intestinal niche. However, it is more difficult to ascertain that microbes have no effect on the host, so as to be described as commensals.

Symbiosis

Originated from the Greek words syn and biosis, meaning “with” and “living”. The original meaning of symbiosis is the “living together of unlike organisms”, first coined in 1879 by the mycologist Heinrich Anton de Bary. The common usage of the term “commensal” should therefore be replaced by “symbiont” to designate the microbiota living within a host. The symbiotic relationships can be formally categorized as mutualistic, commensal, or parasitic, even though parasites are rarely considered symbionts.

Mutualism

Originated from the Latin word mutuus, meaning lent, borrowed, or mutual. A relationship between two organisms where both organisms benefit. For example, bacteria that expand in the intestinal niche and provide metabolic pathways complementing the digestive functions of the host.

Parasitism

Originated from the Greek words para and sitos, meaning “beside” and “food”, or one who eats at another's table. A relationship between two organisms where one organism benefits at the expense of the other. Defines the behavior of a pathogen.