Examination of Host Defense Factors Responsible for Experimental Chronic Respiratory Tract Infection Caused by Klebsiella pneumoniae in Mice

Abstract

We have studied the host defense factors that operate during the course of chronic respiratory tract infection caused by Klebsiella pneumoniae 27 in CBA/J mice. A large number of polymorphonuclear leukocytes (PMNs) rapidly infiltrated the alveolar spaces after infection.Treatment with cyclophosphamide (CY) before infection greatly reduced the infiltration of PMNs and caused an increase in bacterial counts.CY treatment of mice in the chronic phase also caused bacterial proliferation in the lungs. The administration of a high titer immune serum efficiently reduced the bacterial counts in the lungs during the early phase but not during the chronic phase.The proliferation of bacteria induced by CY treatment was not suppressed by the administration of the immune serum in either phase. When the mice were exposed to an aerosol containing Pseudomonas aeruginosa P9 in the chronic phase, the organisms from the secondary infection were eliminated from the lungs in the same manner as in the case of primary infection with P. aeruginosa. Thus, PMNs seem to play an important role in the suppression of bacterial proliferation in the early and chronic phases, and the specific antibody might have a supplementary effect on the defensive action of PMNs in the chronic phase.It is also presumed that the bacteria in the chronic phase of infection are sequestered at sites hardly accessible to PMNs.Although many antimicrobial agents are now available, chronic infections are still difficult to cure. Chronic infection models are therefore required to examine the host-parasite relationship in the chronic phase.We have previously established a model of chronic respiratory tract infection in mice caused by Klebsiella pneumoniae (11). The course of infection in this model is highly reproducible, and the bacterial counts in the lungs after infection change with time, showing four different phases. In the first phase, the bacterial counts decrease for 4 days. In the second phase, the bacterial counts increase starting day 4 and reaching the initial level 1 week after infection. The third phase lasts from 1 week to 4 weeks after infection, during which time the bacterial counts remain relatively unchanged. The fourth phase starts 4 weeks after infection, and thereafter the bacterial counts gradually increase. This model is useful for analyzing 615

Natural Pathogens of Laboratory Mice, Rats, and Rabbits and Their Effects on Research

“…The majority of clinical K. pneumoniae isolates produce a high-molecular-weight capsular polysaccharide, which is one of the dominant virulence factors (289). Immunity is age related (708); is directed against lipopolysaccharide (LPS) and related antigens (542); involves interleukin-1 (IL-1) (693), IL-8 (692), IL-12 (250), leukotrienes (19), chemokines (613), tumor necrosis factor (TNF) (381), TNF-␣-mediated mast cell chemoattraction (417) (which may be influenced by macrophage inflammatory protein type 2 [252]), neutrophil activity (315), and production of defensins (357); and may be inhibited by IL-10 (251). Rats and/or mice infected with or exposed to products from K. pneumoniae serve as models of pneumonia (106,290), endotoxemia (480,686), sepsis (163,293), cystitis and pyelonephritis (87), antibiotic pharmacokinetics (174,265), host resistance (418), riboflavin metabolism (72,537), and human phacoantigenic uveitis (738).…”