13The expression of key defense genes was detected in roots and leaves of tomato 14 plants until the 12 th day after treatments with a mixture of beneficial bio-control agents 15 (BCAs), as soil-drenches. The expression of the same genes was monitored in pre-16 treated plants at the 3 rd and 7 th day since the inoculation with the root-knot nematode 17 Meloidogyne incognita. Genes dependent on SA-signaling, such as the Pathogenesis 18 Related Genes, PR1, PR3, and PR5, were systemically over-expressed at the earliest 19 stages of BCA-root interaction. BCA pre-treatment primed plants against root-knot 20 nematodes. The expression of PR-genes and of the gene encoding for the enzyme 1-21 aminocyclopropane-1-carboxylic acid (ACC) oxidase (ACO), which catalyzes the last 22 step of ethylene biosynthesis, was systemically enhanced after nematode inoculation 23 in primed plants. Defense related enzyme activities, such as endochitinase and 24 glucanase, were higher in roots of BCA-treated than in those of untreated plants, as 25 well. On the contrary, the expression of genes dependent on JA/ET-signaling, such as 26 Jasmonate Ethylene Response Factor 3 (JERF3), did not increase after nematode 27 inoculation in primed plants. The antioxidant system, as indicated by catalase gene 28 expression and ascorbate peroxidase activity, was repressed in infected colonized 29 roots. Therefore, Systemic Acquired Resistance (SAR), and not Induced Systemic30Resistance (ISR), is proposed as the molecular signaling that is activated by BCA 31 priming at the earliest stages of root-nematode interaction. Such BCA-induced 32 activation of the plant immune system did not directly act against nematode motile 33 juveniles penetrating and moving inside the roots. It resulted in a drastically decreased 34 number of sedentary individuals and, then, in an augmented ability of the plants to 35 contrast feeding site building by invasive juveniles. 37 Bio-control agents (BCAs) are beneficial soil-borne micro-organisms that 38 interact with roots and improve plant health. These root-associated mutualists 39 can be divided into three main groups: Bio-control Fungi (BCF), Arbuscular 40 Mycorrhizal Fungi (AMF), and Plant Growth Promoting Rhizobacteria (PGPR) 41 [1, 2]. BCF include the well-studiedTrichoderma spp.,a class of opportunistic 42 fungi that may colonize roots of most plants, reducing the infection of plant 43 pathogens and parasites and promoting positive responses in stressed plants. 44 AMF are obligate root symbionts, diffused in most of the soils, that improve 45 plant growth and can alleviate both abiotic and biotic plant stresses. Several 46 genera of the rhizosphere bacteria, such as Pseudomonas spp., Bacillus spp., 47 and Streptomyces spp., can enhance plant growth and improve health. BCAs 48 can suppress pests and diseases by activation of plant immune system [1, 2, 3, 49 4, 5, 6]. 50 Immune response in plants is regulated by several low molecular weight 51 molecules known as phytohormones, i.e. salicylic ac...