Mitogenic stimulation of murine spleen cells: relation to susceptibility to Salmonella infection

Abstract

The screening of several inbred strains of mice suggested that the capacity of their spleen cells to respond to the mitogenic effect of lipopolysaccharide (LPS) of gram-negative bacteria was correlated with their resistance to intraperitoneal infection with Salmonella typhimurium. An injection of LPS into mice caused changes in the in vitro responsiveness of their spleen cells to the mitogenic effects of LPS and phytohemagglutinin. Pretreatment of mice with whole ultraviolet (UV)-killed bacteria led to a marked rise in the in vitro response of the spleen cells to UV-killed bacteria, but not to LPS or phytohemagglutinin. This enhanced response to UV-killed bacteria was not specific for the 0 antigens of the bacteria.

Dissociation of innate susceptibility to Salmonella infection and endotoxin responsiveness in C3HeB/FeJ mice and other strains in the C3H lineage

“…Thus, animals which are more susceptible to the toxic effects of endotoxin do not die with lower numbers of Salmonella organisms in their organs, a finding which argues against the hypothesis that endotoxin is a major factor in death from Salmonella infection. These results substantiate those of other investigators who have also failed to find a significant role for endotoxin in the pathogenesis of Salmonella infection in mice of disparate lineages (22,29,30) or in humans (7). An additional observation mitigating against the thesis that endotoxin plays a substantive role in all gram-negative infections is the finding that C3H/HeJ mice are more resistant to Escherichia coli peritonitis than are endotoxin-sensitive A/HeJ mice (27).…”

“…Salmonella susceptibility of these two strains has also been reported by Misfeldt and Johnson (12,13). It is noteworthy that von Jeney et al (30), in a study comparing the mitogenicity and Salmonella susceptibility of a variety of inbred mouse strains, reported that C3H.SW mice were mitogenic responders, but had an LD50 of 80 cells, and that C3H/DiSn mice were also mitogenic responders, with an LD50 of 120 cells. Thus, it appears that there are other mouse strains in the C3H lineage, in addition to the ones we have tested, which show an intermediate susceptibility to Salmonella infection as well as mitogenic responsiveness to LPS.…”

“…The relationship is of interest for discerning whether these two phenomena are under the same type of genetic control and for clarifying the role of endotoxin in the pathogenesis of Salmonella infections. Several laboratories have shown that C3H/HeJ mice are hypersusceptible to Salmonella infection (14,17,30), whereas other mouse strains in the C3H lineage, such as C3HMf, C3H/DiSn, C3H/ HeN, C3H/St, and C3H/BiMA, are resistant, but respond normally to the mitogenic and toxic effects of PW-LPS (14,30). These observations have led to the suggestion that there is an inverse relationship between endotoxin responsiveness and Salmonella suceptibility (14,30), a hypothesis which is consistent with the work of Hill et al, who dissociated susceptibility to Salmonella infection from endotoxin lethality by selective breeding (10).…”

In Vitro Proliferative Activity of Spleen Cells in Mice Infected with Attenuated Salmonella typhimurium

“…As proliferation of lymphocytes is an ordinary event in vivo and in vitro and immunological stimuli intensify their proliferation, it is possible that some of the immunological capabilities of lymphocytes are associated intimately with their proliferative capacity. Jeney et al reported (6) that in vitro proliferative responses of the spleen cells obtained from inbred strains of mice to LPS correlated with their natural resistance to infection with S. typhimurium, although the reason the proliferative response of B-lymphocytes to this bacterial cell wall component is associated with the resistance to these intracellular parasites was not indicated.…”

Vaccination Management of Beef Cattle

“…For example, genetically altered mice that do not respond to LPS have been reported to be more susceptible to bacterial infections. 61 Therefore, exposure to small quantities of LPS typically aids immune function and may be beneficial in eliminating pathogens by increasing effector capacities of macrophages and other leukocytes. Conversely, when greater endotoxin exposure occurs because of, for example, mishandling of vaccines or endotoxin stacking, the effect can be detrimental due to varying degrees of sepsis related to bacteremia and endotoxemia.…”