Chronic crop diseases caused by uncultured, obligate, or host-dependent pathogens challenge traditional pathogen-centric paradigms that often interpret symptoms as direct outcomes of pathogen toxins, effectors, or tissue colonization. Here, we advance a host-centric immune framework that reframes disease as an emergent consequence of dysregulated host immune network activity, including prolonged activation, signaling miscoordination, and systemic physiological disruption. Using citrus huanglongbing (HLB) as a primary exemplar and canola clubroot as a parallel system, we synthesize evidence that persistent immune stimulation can drive self-damaging outputs, including sustained reactive oxygen species accumulation, chronic vascular and transport dysfunction, hormone imbalance, and growth–defense trade-offs. While many observations derive from transcriptomic, physiological, and genetic studies conducted under controlled experimental conditions, the available evidence collectively suggests that persistent immune activation may contribute substantially to disease-associated decline in these systems. We argue that pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) operate as an integrated immune network whose feedback structure can become destabilized under chronic infection, generating immune states that are simultaneously harmful and often ineffective at pathogen clearance. We further discuss how panomic profiling, spatially resolved analyses, and network inference can diagnose host immune states at tissue and cell-type resolution, and how genome editing enables causal tests and rational immune tuning strategies that optimize defense amplitude, timing, and localization rather than indiscriminately amplifying resistance. By centering the host immune system as both a source of protection and pathology, this framework provides a conceptual and practical roadmap for understanding and engineering resilience in HLB, clubroot, and other chronic crop diseases in which pathogen biology remains experimentally opaque.
Hu et al. (Mon,) studied this question.