•Piriformospora indica mediate host resistance against early blight by priming of a versatile host-signaling component.•P. indica modulate downstream defense related genes.•P. indica primed transcriptome reprogramming fine tunes jasmonate/ethylene mediated basal defense against pathogen infection. Piriformospora indica is an adaptable mycorrhiza-like fungus belonging to the Sebacinales order that can colonize roots of a wide range of plant species. Studies have shown that P. indica improves growth and enhances systemic defense against pathogens in host plants. However, the mechanism(s) through which these effects occur remain unclear. Therefore to gain more insight into the molecular basis of P. indica induced resistance, cDNA-AFLP (Amplified fragment length polymorphism) based transcript profiling was done to identify differentially expressed genes in P. indica-colonized tomato plants infected with Alternaria solani. Our results demonstrated that pre-colonization of tomato roots with P. indica systemically induced resistance against early blight. Transcript profiling of P. indica pre-colonized tomato plants revealed systemic modulation of several key components of signaling network transcriptional regulators including CBL-interacting protein kinase (CIPK), Mitogen activated protein kinases (MPKs), Lipid transfer proteins (LTPs), WRKY1, ethylene responsive transcription factors (ERF), and Jasmonate Zim Domain 1 (JAZ1), a negative regulator of jasmonic acid (JA) signaling. Expression of downstream defense related genes like Thaumatin-like protein, β-1, 3-glucanase and chitinases was also affected in leaves upon challenge inoculation with pathogen. Interestingly, P. indica pre-colonization alone was unable to induce transcript levels for most of the genes studied. However, pathogen attack on P. indica pre-colonized plants induced strong defense responses. In conclusion, P. indica induces transcriptome reprogramming in a manner that allows rapid and efficient activation of JA/ET (jasmonic acid/ethylene)-mediated basal defenses against pathogen infection by altering the expression of JA/ET related genes. P. indica colonization appears to potentiate the complete signal transduction cascade leading to the systemic expression of defense genes against foliar pathogens. It thus presents itself as a potential and sustainable method of activating multiple components of defense signaling thereby conveying durable horizontal defense against a range of pathogens.