Immune dysfunction due to microgravity remains a hurdle in the next step of human space exploration. Dendritic cells (DC) represent a critical component of immunity, given their role in the detection of invaders and the subsequent task of activating T cells to respond and eliminate the threat. Upon encounter with microbes, DC undergo a process of maturation, whereby the cells upregulate the expression of surface proteins and secrete cytokines, both required for the optimal activation of CD4+ and CD8+ T cells. In this study, DC were cultured from 2–14 days in a rotary cell culture system, which generates a simulated microgravity (SMG) environment, and then the cells were assessed for maturation status and the capacity to activate T cells. Short-term culture (<72 h) of DC in SMG resulted in an increased expression of surface proteins associated with maturation and interleukin-6 production. Subsequently, the SMG exposed DC were superior to Static control DC at activating both CD4+ and CD8+ T cells as measured by interleukin-2 and interferon-γ production, respectively. However, long-term culture (4–14 d) of DC in SMG reduced the expression of maturation markers and the capacity to activate T cells as compared to Static DC controls.

No abstract

During Ebola virus (EBOV) infection, secreted glycoprotein (sGP) is found in large quantities in the serum of both patients and infected animal models. It is thought to serve as a decoy for anti-EBOV antibodies. Using an in vitro model incorporating treatment of non-infected human THP-1 macrophages with recombinant EBOV sGP, this study sought to examine the impact of sGP upon key macrophage functions. Macrophage polarization and phagocytic capacity of activated macrophages were found to be unaltered by sGP treatment. However, treatment with sGP inhibited macrophage production of the pro-inflammatory cytokines TNFα and IL-6 while the yield of anti-inflammatory cytokine, IL-10, remained intact. Interestingly, the migratory ability of macrophages was also diminished by sGP, potentially due to a decrease in expression of CD11b, a vital macrophage integrin. Thus, EBOV sGP may operate to diminish functional contributions of non-infected macrophages to increase the potential viral dissemination.

No human has returned to the moon since the end of the Apollo program 47 years ago, however, new missions are planned for an orbital outpost. Space radiation and the potential for cancer remain as important issues to the future of human space exploration. While improved shield technologies and protective biologicals are under development, little is known concerning the interaction between cancer cells and host immunity in microgravity. As a hallmark of cancer, tumor cells employ mechanisms of immune evasion to avoid elimination by protective CD4+ and CD8+ T cells. We showed that a murine lymphoma was able to produce a soluble factor that inhibited the function of dendritic cells in activating the CD4+ T cells. Culture of the lymphoma cells in simulated microgravity (SMG), and not Static conditions, restored the CD4+ T cell response and augmented CD8+ T cell-mediated destruction of the cancer cells in vitro and in vivo. Thus, SMG impaired the mechanism of tumor escape and rendered the cancer cells more susceptible to T cell-mediated elimination. The stress of microgravity may expose the most critical components of a tumor’s escape mechanism for astronaut protection and the generation of new cancer therapeutics for patients on Earth.

One of the major concerns of long-duration spaceflight is the exposure of astronauts to space radiation and the potential for cancer development. Natural killer (NK) cells continuously survey the body for such abnormalities and upon detection are activated to produce pro-inflammatory cytokines as well as cytotoxins which induce apoptosis of the cancer cells. This study employed the rotary cell culture system to generate a simulated microgravity (SMG) environment in order to assess its effect upon the growth of human cancer cells and their susceptibility to lysis by NK cells. We found that SMG diminishes the numbers of both pancreatic cancer cells and NK92MI, a human NK cell line, over a 7 d culture period. Additionally, SMG NK92MI cells had a ~50% decrease in cytotoxicity against PANC-1 pancreatic cancer cells. Surprisingly, a long-term SMG culture of up to 14 d resulted in complete restoration of NK92MI cell cytotoxic function. Interestingly, SMG cultured NK92MI cells produced more IFN-gamma than Static NK cells throughout the time periods assessed. In comparison, 7 d culture of pancreatic cancer cells in SMG led to a ~50% reduction in the ability of either Static or SMG NK92MI cells to induce apoptosis in the SMG cultured cancer cells. Therefore, over a two-week period in SMG culture, NK92MI cells were able to adapt to the environment and recover cytotoxic function, however, pancreatic cancer cells cultured in SMG acquired resistance to lysis by the NK cells. Hence, cancer cells developing in astronauts in microgravity might have a greater potential to resist NK cell control than in patients here on Earth which upon elucidation may aid in the identification of relevant new tumor targets for therapeutics.