Evolution of Th2 immunity: a rapid repair response to tissue destructive pathogens.

摘要: Throughout evolutionary history, animals have faced attack byfellow metazoans, often resulting in damage to tissues. This cantake the form of a worm migrating find its reproductive niche oreating host tissue for food, or even bite an insect. A pro-inflammatory oxidative-type immunological attack, typicallyutilized against intracellular microbes, can some cases kill thesemulticellular parasites [1], but because worms and insects cannotbe contained within single cell, collateral thatwill result from such could seriously compromise hostfitness. During course evolution, most cost-effectiveapproach deal with very large foreign invaders may beento tolerate them quickly repair any thatcompromised fitness [2,3]. In this scenario, Th1 immunitycharacterized by IFN-c production evolved control our innateanti-microbial pathways, while defense system thatevolved cope metazoan was innate tissuerepair process, now controlled Th2 cells. cells subsequentlyevolved additional mechanisms contain expel theoffending element produce cytokines as IL-4, IL-5, IL-10, IL-13 that promote alternative macrophage activation,eosinophil maturation recruitment, IgE production, toname just few [4]. Many these processes the‘‘walling off’’ bodies through granuloma formation andmatrix deposition, which would quite naturally follow frommechanisms close open wounds.Evolutionary hypotheses are difficult prove, murinestudies helminth infection provide ‘‘modern’’ evidence thattissue orchestrated is primary defenseagainst metazoa. As illustrated Figure 1 Schistosoma mansoni,metazoan literally tear important barriers, ofteninducing micro-hemorrhages multiple organsas they complete their life cycle (Figure 1). Strikingly, S. mansoniinfection IL-4Ra-deficient lack effectorresponses results lethal sepsis once eggs produced themesenteric blood vessels cross intestinal wall [5]. suggeststhat IL-4Ra-mediated pathways critically needed maintaingut integrity prevent leakage luminal dwelling bacteria intothe blood. similar scenario plays out during infections manygut nematodes, broad-spectrum antibiotics providing at leastpartial protection when IL-4Ra-driven barrierimmunity impaired [6].The cardinal features adaptive immunity memory andantigen-specificity. Since part adaptiveimmune system, raises question why we need to‘‘remember’’ wounds induced specificparasites. hookworm causes bleeding it migrates thelung then penetrates gut feed. parasite-specificmemory cell might accelerate wound closure, significantlyreducing detrimental effects on secondary exposures. Indeed,adaptive be equally fortolerance minimize forresistance pathogen itself [3,7]. To date, no experimentshave directly addressed whether faster asecondary encounter same injuring agent. However,there suggest hemorrhaging reduced onsecondary lung-migrating nematodes (GrahamLeGros, personal communication).Helminths, best-described inducers cytokines,include animal phyla diverged over billionyears ago, increasing suggests insect bites arealso Th2-inducers [8,9]. Thus, appears hard-wiredto mount responses pathogen.Tissue destruction common feature parasites, weare proposing mechanism heals inflict. Theseevolutionary principles, if true, must apply beyond mammals.Infection Atlantic salmon sea lice gross skin lesionsthat rapidly healed, break osmoticshock aqueous environment. Activated migrate tothe site attachment mediate essential thelesion also expulsion ectoparasite [10]. Importantly, ananti-wounding response not unique vertebrates, one thefitness advantages provided immune mayhave been ability needed, tomediate parasite-specific tolerance [3].