Increased susceptibility to Pseudomonas aeruginosa infection under hindlimb-unloading conditions

Abstract

It has been reported that spaceflight conditions alter the immune system and resistance to infection [Belay T, Aviles H, Vance M, Fountain K, and Sonnenfeld G. J Allergy Clin Immunol 170: 262-268, 2002; Hankins WR and Ziegelschmid JF. In: Biomedical Results of Apollo. Washington, DC: NASA, 1975, p. 43-81. (NASA Spec. Rep. SP-368)]. Ground-based models, including the hindlimb-unloading model, have become important tools for increasing understanding of how spaceflight conditions can influence physiology. The objective of the present study was to determine the effect of hindlimb unloading on the susceptibility of mice to Pseudomonas aeruginosa infection. Hindlimb-unloaded and control mice were subcutaneously infected with 1 LD50 of P. aeruginosa. Survival, bacterial organ load, and antibody and corticosterone levels were compared among the groups. Hindlimb unloading had detrimental effects for infected mice. Animals in the hindlimb-unloaded group, compared with controls, 1). showed significantly increased mortality and reduced time to death, 2). had increased levels of corticosterone, and 3). were much less able to clear bacteria from the organs. These results suggest that hindlimb unloading may induce the production of corticosterone, which may play a critical role in the modulation of the immune system leading to increased susceptibility to P. aeruginosa infection.

Active hexose correlated compound enhances the immune function of mice in the hindlimb-unloading model of spaceflight conditions

“…Our laboratory has shown, in previous studies, that hindlimb unloading of mice decreases resistance to infection (4,8,17) and that the use of countermeasures reduces these effects in this model (5). Hindlimb-unloaded mice were far more susceptible than control mice to infection with Klebsiella pneumoniae (8) and Pseudomonas aeruginosa (4).…”

“…The acetylated forms of the last group are oligosaccharides with low molecular mass (5 kDa) and are believed to be the molecules responsible for the biological activities of AHCC (27,28,51). AHCC has been shown to have an enhancing effect on the immune system of humans (27) and rodents (10,28,47), including an increase of natural killer cell activity (25) and IL-12 production (49, 50).Our laboratory has shown, in previous studies, that hindlimb unloading of mice decreases resistance to infection (4,8,17) and that the use of countermeasures reduces these effects in this model (5). Hindlimb-unloaded mice were far more susceptible than control mice to infection with Klebsiella pneumoniae (8) and Pseudomonas aeruginosa (4).…”

Transcriptional and Proteomic Responses ofPseudomonas aeruginosaPAO1 to Spaceflight Conditions Involve Hfq Regulation and Reveal a Role for Oxygen

“…Spaceflight has been shown to alter the response of monocytes, isolated from astronauts preflight and in flight, to . Further, simulation of aspects of this microgravity-associated decreased immune response, using the hind limb unloaded mouse model, showed an enhanced susceptibility of these animals to bacterial infection (3,6). From the pathogen's perspective, bacterial obligate and opportunistic pathogens have been found to exhibit enhanced stress resistance phenotypes following growth under both true spaceflight and microgravity analogue conditions (13,30,33,(46)(47)(48)(49).…”

Enhancement of In Vitro Growth of Pathogenic Bacteria by Norepinephrine: Importance of Inoculum Density and Role of Transferrin

“…High circulatory levels of these hormones are detected in individuals exposed to a variety of physically and/or mentally stressful situations, including trauma, space flight, and sepsis (13,29,31,32). The increases not only may alter the immune function but also may contribute to host morbidity and increased risk of infection (1,7,34). In the current study we reexamined the in vitro growth responses of a variety of bacterial species that were previously tested and reported not to be enhanced by the addition of NE (6,8).…”

“…Although a great deal of evidence suggests that stress-induced neurohormones play a critical role in the outcome of infections (1,3,4,5,7,21,31), the mechanisms by which these hormones act in the host remain unclear. Studies with human and animal models have indicated that increased levels of stress hormones, including norepinephrine (NE), as well as other catecholamines, alter the immune response and physiology of the host (2).…”