INNATE IMMUNE ACTIVATION BY Proteus Mirabilis FLAGELLIN IN THE URINARY TRACT

UMPIERREZ, A; SCAVONE, P; ROMANIN, D; RUMBO, M; ZUNINO, P

Lima

Congreso; InmunoPerú 2012; 2012

Asociación Latinoamericana de Inmunología

Proteus mirabilis, Gram negative motile bacillus that overexpresses flagella on its surface is a common cause of complicated urinary tract infections (UTI) in humans. Urinary tract (UT) epithelium is an important mechanic barrier where potent innate immune responses are induced upon recognition of selected microbial ligands. Pattern recognition receptors (PRRs) in the host allows the identification of conserved molecular associated microbe patterns (MAMPs) like flagellin, the structural component of flagella. The interaction with flagellin, results in NF-κβ pathway activation and proinflammatory gene expression. Therefore, innate immune response modulation in the UT has important implications counteracting UTI development. The objective of this work was to analyze P. mirabilis flagellin capacity to induce an innate immune response trough different approaches. For innate immune activation, P. mirabilis flagellins purified from different clinical UTI isolates were evaluated using the CacoCCL20-Luc reporter system. Chemokine expression was evaluated in T24 human epithelial bladder cell line cultures, after stimulation with flagellin. In order to evaluate in vivo immune response, animals were transurethrally instilled with flagellin. Immune cell counts in urine were determined using a Neubauer chamber and bladder histological modifications were microscopically examined. We observed that purified P. mirabilis flagellins had different capacities to activate the CacoCCL20-Luc system, been almost all stimulating proteins. Also, incubation of T24 cells with flagellin induced a significant increase of proinflammatory CCL20, CXCL2 and MCP-1 mRNA expression respect to non-treated cells (37,1.5 and 5.1 respectively). Urine cell counts and bladder histological modification score of treated bladders were higher than control bladders (p