Susceptibility of NOD/scid IL-2Rγnull mice inoculated with alcoholic patient white blood cells to the pulmonary infection of Klebsiella pneumoniae (HUM8P.331)

Abstract

Abstract Alcoholics are known to be very susceptible to various opportunistic infections. In this study, host antibacterial resistance of alcoholics to K. pneumoniae infection was characterized in a murine chimera model of alcoholics. A chimera model of alcoholics (patient chimeras) was created in NOD/scid IL-2Rγnull mice irradiated with γ-rays (3.5 Gy) after inoculation with WBC (5 x 106 cells) from alcoholic patients. As a control (healthy chimeras), the same scid mice were inoculated with 5 x 106 cells of healthy donor WBC. Both chimeras were intratracheally infected with K. pneumoniae (100 CFU). In the results, bacterial growth was detected in the lungs and kidneys of patient chimeras, while significant numbers of bacteria were not isolated from these organs of healthy chimeras. All patient chimeras died within 2 days of infection, while 75% of healthy chimeras survived more than 7 days after the infection. Alcoholic patient CD14+ cells killed K. pneumoniae, while the pathogen was not killed by the same cells isolated from healthy donors. CD14+ cells isolated from WBC of alcoholic patients were shown to be IL-10-producing CCL1+CD163+ cells (M2bMφ), while these cells were not isolated from WBC of healthy donors. These results indicate that host antibacterial resistance is not displayed in humanized chimeras created with alcoholic patient WBC. M2bMφ demonstrated in alcoholic patient WBC may play a role on the impaired resistance of alcoholics to opportunistic infections.