Increased Susceptibility to Escherichia coli Infection in Mice Pretreated with Corynebacterium parvum

Abstract

The contribution of activated macrophages to protection against Escherichia coli was studied in mice treated intravenously with Corynebacterium paruum 7 days before infection. C. parvum-treated mice showed increased phagocytic activity and enhanced resistance to Listeria infection. In contrast, these mice showed increased susceptibility to a subsequent challenge with E. coli that correlated closely with a reduction in the LDso of lipopolysaccharide (LPS) in these mice. The peritoneal macrophages obtained from C. parvum-treated mice had a strong ability to phagocytize and kill E. coli in in vitro experiments. A rapid decline in the number of bacteria in the liver of C. parvum-treated mice was observed in the early period ofinfection. However, the number of bacteria in liver and spleen increased progressively to a lethal dose from 6 hr after infection. At this time, a significant increase in ,a-glucuronidase, a lysosomal acid hydrolase, was found in the serum of these mice. In vitro experiments revealed that the peritoneal macrophages from C. parvum-treated mice were highly susceptible to the cytotoxic effect of LPS after 6 hr of incubation with LPS. It is suggested that the hypersensitivity of activated macrophages to the cytotoxic effect of endotoxin derived from E. coli may be partly responsible for the increased susceptibility of C. parvum-treated mice to E. coli infection.There are distinct morphological and functional differences between polymorphonuclear cells (PMN) and macrophages, although both cell types are known to play important roles in the protection against infection with a variety of bacteria (2, 6, 17). PMN are reported to be important for host resistance against Pseudomonas aeruginosa (24) and Escherichia coli (23), whereas macrophages playa protective role in the early stage of infection with Listeria monocytogenes (II).Macrophages activated by killed Corynebacterium parvum have been shown to have a high level of lysosomal enzyme activity and an increased capacity to generate oxygen radicals as much as or even more than PMN (12). However, it is not known whether activated macrophages contribute to the host resistance to E. coli infection which depends mainly on the function of PMN.In the present study, the effect of pretreatment of mice with C. parvum on E. coli infection was investigated in an attempt to determine the role of nonspecifically activated macrophages in protection against E. coli infection. Our results show an 273

Enhanced resistance to Gram-positive bacterium and increased susceptibility to bacterial endotoxin in mice sensitized withPropionibacterium acnes: involvement of Toll-like receptor

“…It has been known that mice sensitized with Propionibacterium acnes exhibit an enhanced susceptibility to endotoxin as determined by mortality or severe hepatic injury after injection of bacterial lipopolysaccharide (LPS), the major outer membrane component of Gram‐negative bacteria [1]. An impaired resistance to infection with Escherichia coli , a Gram‐negative bacterium, was also reported [2]. In contrast to this detrimental effect, P. acnes treatment greatly enhance the protection of mice against lethal infection with Listeria monocytogenes , a Gram‐positive bacterium [3].…”

Increased sensitivity of Corynebacterium parvum-treated mice to toxic effects of indomethacin and lipopolysaccharide

“…In contrast, macrophages from C. parvum-treated mice have been reported to exhibit enhanced sensitivity to the toxic effects of LPS (29). Yoshikai et al (29) have reported that incubation of peritoneal macrophages from C. parvumtreated mice with concentrations of LPS which were nontoxic to macrophages from control mice leads to greater than 50% cell death by 6 h. They suggested that this effect may be at least partially responsible for the increased sensitivity of C. parvum-treated mice to the lethal effects of LPS. Ferluga et al (7) have also reported that C. parvum-treated BALB/c mice were highly susceptible to the toxic effects of LPS.…”

“…In contrast, Vogel et al (25) reported that BCG treatment of C3H/HeJ mice leads to a lowering of the 50% lethal dose for E. coli LPS from >8 mg to 282 ,ug. Similar experiments with C. parvum have revealed that treated mice exhibit enhanced sensitivity to other bacteria (29) as well as bacterial products such as LPS (3,7,29). Several authors (discussed in references 3, 21, and 29) have concluded that the macrophage may play a central role in these altered responses to LPS.…”

The influence of killed Propionibacterium granulosum on experimental infection with Escherichia coli

“…1), it can be assumed that the reticulo-endothelial system is involved in resistance to E. coli infection. It has been doubted, whether macrophages play a distinct role in resistance to E. coli infection (Yoshikai et al 1983). These authors have even reported an increased susceptibility of mice pretreated with C. parvurn to infection with E. coll.…”