Characteristics of human dendritic cells generated in a microgravity analog culture system

Abstract

Generation of an effective immune response requires that antigens be processed and presented to T lymphocytes by antigen-presenting cells, the most efficient of which are dendritic cells (DC). Because of their influence on both the innate and the acquired arms of immunity, a defect in DC would be expected to result in a broad impairment of immune function, not unlike that observed in astronauts during or after space flight. In the study reported here, we investigated whether DC generation and function are altered in a culture environment that models microgravity, i.e., the rotary-cell culture system (RCCS). We observed that RCCS supported the generation of DC identified by morphology, phenotype (HLA-DR+ and lacking lineage-associated markers), and function (high allostimulatory activity). However, the yield of DC from RCCS was significantly lower than that from static cultures. RCCS-generated DC were less able to phagocytose Aspergillus fumigatus conidia and expressed a lower density of surface HLA-DR. The proportion of DC expressing CD80 was also significantly reduced in RCCS compared to static cultures. When exposed to fungal antigens, RCCS-generated DC produced lower levels of interleukin-12 and failed to upregulate some costimulatory/adhesion molecules involved in antigen presentation. These data suggest that DC generation, and some functions needed to mount an effective immune response to pathogens, may be disturbed in the microgravity environment of space.

Physiological, Pharmacokinetic, and Pharmacodynamic Changes in Space

“…However, simulated microgravity induces some important changes as well, therefore indicating that microgravity itself is a major component of these changes. 92,[104][105][106][107] A recent study in simulated microgravity has shown a significant inhibition in peripheral blood lymphocytes apoptosis, 106 which is in contrast with the results from STS-80 and STS-95, in which an increase was observed. 99 A study by Chouker and collaborators 107 in simulated microgravity showed an increase in the number of circulating natural killers but no change in T cells and lymphocytes, although the ratio of T helper to T cytotoxic and T suppressor cells was decreased.…”

“…The yield of DC cultured in a RWCCS was shown to be lower than that of static controls. 105 In addition, DC from the RWCCS were less able to phagocytose Aspergillus fumigatus conidia, produced lower levels of interleukin-12, and expressed a lower density of surface HLA-DR. 105 A defect in DC would be expected to result in a broad impairment of immune function.…”

“…Activity of lymphocytes has been shown to decrease. 104,105 Simulated microgravity was shown to alter the respiratory burst activity in nonadherent promyelocytic cells. If this is confirmed to happen in true microgravity, the recovery from infections during space flight could be delayed.…”

Considerations for non-invasive in-flight monitoring of astronaut immune status with potential use of MEMS and NEMS devices

“…These analog systems help to gather a basic understanding of behavioral trends of cells in space; however, they cannot completely simulate the complexity of the interactions within the dynamic systems of a human or animal, and are not discussed in depth here. Cogoli (1996), Hashemi et al (1999), Bakos et al (2001), Savary et al (2001) and Borchers et al (2002) provide reviews of immune related cell culture studies relevant to space flight.…”

Hypergravity Effects on Dendritic Cells and Vascular Wall Interactions

“…Unfortunately, in front of many studies on lymphocytes (Cogoli 1997) and endothelial cells (Morbidelli et al 2005), the behaviour of DCs in hypo-and hypergravity is quite completely unknown. Recent studies demonstrated that DCs are sensitive to microgravity conditions, both real and modelled, which impair DC differentiation from monocytes (Savary et al 2001;Monici et al 2007).…”