We developed an acute melioidosis model in BALB c mice to get a comprehensive genome wide view of the host transcriptional response during the acute stage of melioidosis. Our analyses clearly demonstrated that the pathogen had intimately engaged the innate immune system at the early onset of infection by rapid induction of numerous inflammatory responses. The primary Inhibitors,Modulators,Libraries response observed was the overwhelming induction of TLR2 to counteract B. pseudomallei, which we propose, subsequently triggered the activation of many inflammation biased genes important in attracting neutrophils and monocytes to the site of acute inflam mation. These cytokines and chemokines also function as central mediators in activating various host defence systems such as apoptosis, JAK STAT signalling path way, mitogen activated protein kinase signalling pathway and ultimately trigger the appropriate adaptive immune system.

Induction of these genes was previously reported in numerous in vivo, in vitro or melioidosis patient studies. Hence our study rein forces the consistency of the Inhibitors,Modulators,Libraries inflammatory genes expres sion in response to acute melioidosis. Concomitantly, the host frontline defence system is boosted by increas ing the production of granulocytes. Neverthe less, the bacteria are capable of propagating in a tissue environment Brefeldin_A that is evidently overloaded with high levels of inflammatory associated proteins. This genome wide expression study confirms that the production of signals responsible for the activation of pro inflammatory genes in response to B. pseudomallei infection, are mainly TLR2 dependent.

This observation supports a previous finding of improved survival in respiratory infection in TLR2 KO mice with reduced bacterial burden and lung inflammation, as well as less distant organ injury. The cluster of inflammatory associated Inhibitors,Modulators,Libraries genes consis tently highly induced in response to B. pseudomallei acute infection is part of the group designated as com mon host immune response. Most of these genes are induced in many different cell types in response to exposure to several different pathogen species such as Escherichia coli, Salmonella typhi, Staphylococcus Inhibitors,Modulators,Libraries aur eus, Listeria monocytogenes, Mycobacterium tuberculosis, Candida albicans, Bordetella pertussis, Mycobacterium bovis, P. aeruginosa and S. typhimurium. Up regulation of this core set of genes by pathogens might represent a general alarm signal for inflammatory infections. Common host genes known to be repressed by pathogens have been identified in PBMCs infected with B. pertussis, E. coli and S. aureus. Surprisingly in our study, these genes were highly induced in response to B. pseudomal lei infection and could be a Burkholderia specific response.