The Neuro‑immune Interface in Invertebrate Disease Tolerance: From Signaling Pathways to Evolutionary Strategies

Infectious diseases pose a major challenge to animal survival. Host responses fall into two broad categories: resistance (reducing pathogen load) and tolerance (limiting tissue damage without eliminating the pathogen). While resistance mechanisms are well understood, the neuro‑immune foundations of disease tolerance remain largely unexplored, particularly in invertebrates. This review synthesizes growing evidence that the invertebrate nervous system regulates behavioral and humoral immune responses to achieve disease tolerance through conserved signaling pathways, including biogenic amines, neuropeptides, and TRP channels. Key model organisms such as Drosophila melanogaster and Caenorhabditis elegans reveal pivotal roles for anorexia, sleep alterations, behavioral fever, and gustatory avoidance in promoting tolerance. Moreover, interspecies variation in the expression of sickness behaviors offers important evolutionary insights. This review highlights tolerance as an ancient, complementary strategy to resistance and identifies current research gaps. Understanding the neuro‑immune interface in invertebrates not only deepens our knowledge of immune evolution but also opens new avenues for disease management in agriculture and pollinator conservation.

کلیدواژه ها:

Disease tolerance ، Neuro‑immune interface ، Invertebrates ، Sickness behaviors ، Infection resistance