Danger, Microbes, And Homeostasis

Danger, Microbes, and Homeostasis Brian P. Lazzaro, et al. Science 332, 43 (2011); DOI: 10.1126/science.1200486

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PERSPECTIVES
IMMUNOLOGY

Danger, Microbes, and Homeostasis
Brian P. Lazzaro1 and Jens Rolff 2

Hosts may modulate their immune response by measuring acombination of signals from pathogens and damaged tissue.

he immune system is conventionally ria, which have enormous importance to the In addition to displaying MAMPs, true viewed as a means to fight infection. It health and physiology of the host (4), main- pathogens stimulate the release of danger has become clear, however, that what tained? Studies in insect model systems sug- signals bydamaging host cells or secreting is considered the “immune” system has also gest that the joint presence of both MAMPs molecules that interfere with host biology. evolved to maintain homeostasis and regulate and danger signals may be required to This combination of MAMPs and danger commensal microbes that normally inhabit launch a true defense response (5) and that signals can override the homeostaticnegathe body. Such varied functions demand insects have mechanisms for disregarding tive regulation of the insect immune system nuanced and context-appropriate control MAMPs presented in the absence of patho- in tissues like the gut, resulting in a fullof immune responses. The thoughts on how logical damage to the host. blown defense response that includes high immunity becomes activated includetwo The animal gut is constantly exposed expression of antibiotic proteins and bioviews: by recognition of “nonself ” molecules to potentially pathogenic bacteria that are chemicals (11–13). Interestingly, the lower of infectious agents (1) or by recognition of ingested along with food. Yet, the gut is level of defense activity triggered even “danger” signals—host molecules released also the mostimportant compartment of by commensals stimulates gut stem cell by damaged host cells (2). Empirical evidence immune-modulated regulation of beneficial activity and epithelial renewal ( 13), supports both models, but also reveals their microbial communities that aid in digestion providing an unexpected mechanism by limits. Insights from recent studies on insect and nutritional assimilation (4).Beneficial which hosts and microbes interact to effect immune systems, which are generalizable to microbes in both vertebrate and insect guts host homeostasis. vertebrates, suggest that the two models may be compatible. That is, a host determines Challenge Elicitors Host Host homeostasis the balance of nonself elicitors and danger signals to decide Wound repair when to activate the immune Wound...