Susceptibility of NOD/scid IL-2Rγnull mice inoculated with alcoholic patient white blood cells to Pseudomonas aeruginosa infection (P3029)

Abstract

Abstract We have previously demonstrated that CCL2+ neutrophils (PMN-II) and IL-12−IL-10+ monocytes (M2 monocytes) are predominated in WBC of alcoholic patients. Since these cells are inhibitory on the generation of major antibacterial effector cells, in this study, we investigated the susceptibility of alcoholic patients to P. aeruginosa infections in a humanized murine model. To create an experimental model of alcoholic patients, 5 x 106 cells of WBC of alcoholic patients were adoptively transferred to X-irradiated-NOD/scid IL-2Rγnull mice. As a control, these mice were inoculated with healthy donor WBC. Then, they were infected s.c. with P. aeruginosa (10 CFU/chimera) and bacteria in liver and kidneys of these chimeras were quantified. In the results, bacteria grew (> 103 CFU/g organ, 24 hrs after infection) in liver and kidneys of the chimeras created with alcoholic patient WBC, while bacteria disappeared within 24 hrs after P. aeruginosa infection from these organs of the control chimeras. CD14+ cells isolated from WBC of alcoholic patients were shown to be IL-10+IL-12−CCL1+ cells, while IL-10−IL-12+CCL1- cells were isolated from healthy donor WBC stimulated with heat-killed P. aeruginosa. These results indicate that chimeras created with alcoholic patient WBC are carriers of M2b monocytes and susceptible to P. aeruginosa infection, while chimeras created with healthy donor WBC are carriers of M1MΦ and resistant against these infections.