Host mixtures are a promising method for agroecological plant disease control. Plant immunity is key to the success of host mixtures against polymorphic pathogen populations. This results from priming-induced cross-protection, whereby plants able to resist infection by specific pathogen genotypes become more resistant to other pathogen genotypes. Strikingly, this phenomenon was thus far absent from mathematical models aiming at designing host mixtures. We developed a model to specifically explore how priming affects the coexistence of two pathogen genotypes in host mixtures composed of two host genotypes, and how it impacts disease prevalence. The main effect of priming is to reduce the coexistence region in the parameter space (due to cross protection), and to generate a singular mixture of resistant/susceptible hosts corresponding to the maximal reduction disease prevalence (in absence of priming, a resistant pure stand is optimal). The epidemiological advantage of host mixtures over a resistant pure stand thus appears as a direct consequence of immune priming. We also showed that there is indirect cross-protection between host genotypes in a mixture. Moreover, the optimal mix prevents the emergence of a resistance-breaking pathogen genotype. Our results highlight the importance of considering immune priming to design optimal and sustainable host mixtures.

It has long been recognized that sustainable agriculture requires profound changes in agricultural practices (Eyhorn et al., 2019). Still, the vast majority of agro-ecosystems are grown as monocultures, that is, as large and continuous deployment of a single plant genotype over potentially vast areas (McDonald & Stukenbrock, 2016). The development of mechanization, plant breeding, and crop protection products promotes the use of monocultures because they facilitate crop management and ensure high yields under current management practices (Wuest et al., 2021).Unfortunately, these homogeneous and simplified agricultural landscapes are particularly vulnerable to disease outbreaks (Brown, 2015), since pathogens are best transmitted in genetically similar environments (Stukenbrock & McDonald, 2008). In addition, genetically identical crops increase the selection pressure toward pathogens overcoming plant resistance. As a result, defeated resistances are no longer of agronomic value, the available genetic diversity is eroding (Thrupp, 2000), and the need for pesticides increases (Brown & Tellier, 2011).Sustainable agriculture requires growers to preserve diversity and reduce inputs within the crops (Renard & Tilman, 2021). In