Changes in monocyte functions of astronauts

Kaur, Indreshpal; Simons, Elizabeth R.; Castro, Victoria; Ott, C. Mark; Pierson, Duane L.

doi:10.1016/j.bbi.2004.12.006

Cited by 149 publications

(115 citation statements)

References 21 publications

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“…From the host point of view, astronauts experience a compromised immune response under spaceflight conditions, as reflected in cellular alterations of both the innate and adaptive immune systems (23,26,40). Spaceflight has been shown to alter the response of monocytes, isolated from astronauts preflight and in flight, to .…”

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confidence: 99%

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

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Monsieurs

et al. 2011

Appl Environ Microbiol

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Assessing bacterial behavior in microgravity is important for risk assessment and prevention of infectious diseases during spaceflight missions. Furthermore, this research field allows the unveiling of novel connections between low-fluid-shear regions encountered by pathogens during their natural infection process and bacterial virulence. This study is the first to characterize the spaceflight-induced global transcriptional and proteomic responses of Pseudomonas aeruginosa, an opportunistic pathogen that is present in the space habitat. P. aeruginosa responded to spaceflight conditions through differential regulation of 167 genes and 28 proteins, with Hfq as a global transcriptional regulator. Since Hfq was also differentially regulated in spaceflight-grown Salmonella enterica serovar Typhimurium, Hfq represents the first spaceflight-induced regulator acting across bacterial species. The major P. aeruginosa virulence-related genes induced in spaceflight were the lecA and lecB lectin genes and the gene for rhamnosyltransferase (rhlA), which is involved in rhamnolipid production. The transcriptional response of spaceflight-grown P. aeruginosa was compared with our previous data for this organism grown in microgravity analogue conditions using the rotating wall vessel (RWV) bioreactor. Interesting similarities were observed, including, among others, similarities with regard to Hfq regulation and oxygen metabolism. While RWV-grown P. aeruginosa mainly induced genes involved in microaerophilic metabolism, P. aeruginosa cultured in spaceflight presumably adopted an anaerobic mode of growth, in which denitrification was most prominent. Whether the observed changes in pathogenesis-related gene expression in response to spaceflight culture could lead to an alteration of virulence in P. aeruginosa remains to be determined and will be important for infectious disease risk assessment and prevention, both during spaceflight missions and for the general public.The microgravity environment associated with spaceflight is unique and has a profound effect on both host and pathogen cells, with potential implications for infectious disease. From the host point of view, astronauts experience a compromised immune response under spaceflight conditions, as reflected in cellular alterations of both the innate and adaptive immune systems (23,26,40). 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). In response to the spaceflight environment, global transcriptional and proteomic changes were observed for the ente...

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confidence: 99%

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

Crabbé

Schurr

Monsieurs

et al. 2011

Appl Environ Microbiol

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152

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“…Recognition of pathogens by receptor-mediated liganding initiates a variety of signals within the phagocyte, detectable within seconds of the stimulus' binding; these signals, in turn, drive the cell towards its eventual effector functions that are intended to include ingestion and killing of the invading organism within cell phagosomes (1-7). Fluorescently labeled particles such as Dextrans (19,22), zymosan (41), Bioparticles TM (42)(43)(44), immune complexes (15)(16)(17)(18)35,41) fixed or dead cells (32) have been used to indicate phagocytosis and/or to distinguish live from dead cells, generally minutes to hours after phagocytosis was initiated. While the probes used for such studies, usually fluorescein or rhodamine derivatives, are somewhat pH sensitive below 7.1, the pH they indicate, if a quantitative evaluation is made, reflects the conditions at that time, i.e., after multiple bactericidal processes have occurred and an equilibrium of sorts has been achieved.…”

Section: Discussionmentioning

confidence: 99%

Initial cytoplasmic and phagosomal consequences of human neutrophil exposure to Staphylococcus epidermidis

2009

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Microorganisms are recognized by specific phagocyte surface receptors. Liganded receptors then signal a series of events leading to phagocytosis and destruction of the organism by oxidative, lytic, and associated processes. Some organisms, such as Mycobacterium tuberculosis (Mtb), Cryptococcus neoformans (Cf), and others, evade such destruction, surviving and sometimes multiplying within the phagosome to later cause disease. To study such evasion, we developed protocols which permit simultaneous kinetic measurement of early cytoplasmic signaling and of phagosomal pH (pH p ) and oxidative burst, on a cell-by-cell basis, of polymorphonuclear (PMN) leukocytes exposed to fluorescently labeled, nonpathogenic Staphylococcus epidermidis (Se). The availability of a new, highly sensitive pH probe, pHrodo TM , permits observation of increasing pH p . Simultaneous labeling of the organism, applicable to any phagocyte target, with a probe insensitive to pH and oxidative species, such as AlexaFluor350 TM , permits distinction between binding and functional responses to it by ratioing fluorescences. Addition of an extracellular-specific quencher (Trypan blue) permits distinction between bound and phagosome-enclosed targets, so that conditions within the closed phagosome can be studied. We found that opsonization is required for functional activation of PMN by Se, that the organism causes early alkalinization of the phagosome (in contrast to Cf which hyperacidifies it), and that extracellular Ca 21 is not required for cytoplasmic Ca 21 signaling but contributes markedly to binding of Se to PMN and to ensuant bactericidal functions. These findings lead to a new approach to the study of select organisms, like Cf and Mtb, which evade killing by manipulating the phagosomal environment. ' International Society for Advancement of CytometryKey terms calcium; pH; reactive oxygen species PHAGOCYTIC cells, such as polymorphonuclear (PMN) neutrophils and tissue macrophages (MP), are essential components of the human innate defense against infection. Phagocyte surface receptors recognize invading bacteria by a variety of mechanisms, including complement-dependent opsonization, antibody/antigen binding via Fc receptors, or pattern recognition (e.g., mannose-, scavenger-, or Toll-) receptor liganding. They then signal, via changes in intracellular cation concentrations, in transmembrane potentials, and in secondary signaling (e.g., via activation of specific phospholipases) so as to initiate a series of processes that result in phagocytosis with subsequent intraphagosomal killing and clearance of the organism [for some very recent reviews see (1-7)].Many of these signaling events occur early, within seconds of ligand-receptor binding, and have been shown to vary with the specific receptors involved (8)(9)(10)(11)(12)(13)(14). Yet, the changes initiated by these signals to generate effector functions of the cell do not become measurable by conventional methods until at least minutes later. Furthermore, responses to such stimulation...

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“…Table 3 summarizes the findings of human immunity during the Space Shuttle era (11)(12)(13)(14)(15). Establishing the medical risk associated with the many changes observed in human immunity proved difficult.…”

Section: A Latent Virus Reactivationmentioning

confidence: 99%

“…Biodegradation of critical materials can result in system failures that may endanger crews. Evidence gained during the SSP suggests that infectious diseases and allergic responses may increase on long exploration missions due to sustained immune deficiencies (11)(12)(13)(14)(15) and increased virulence of some microorganism (7)(8)(9)(10). …”

Section: Identification Of Microbiological Hazards and Risksmentioning

confidence: 99%

“…Some bacteria and fungi were shown to be more virulent as a result of spaceflight (7)(8)(9)(10). Immune studies showed decreases in innate immunity, cell mediated immunity (11)(12)(13)(14)(15), and increased latent virus reactivation (16)(17)(18)(19). The approaches taken to ensure a microbiologically safe and productive environment for astronauts to work and live, along with microbiological monitoring results, various anomalies, and results of major infectious disease related research are discussed.…”

Section: Introductionmentioning

confidence: 99%

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